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  • 1.
    Botling, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Sandelin, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Immune Biomarkers on the Radar-Comprehensive "Immunograms" for Multimodal Treatment Prediction2017In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 12, no 5, p. 770-772Article in journal (Other academic)
  • 2.
    Brännvall, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Sandelin, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Wallenquist, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Forsberg-Nilsson, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Aldskogius, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Neuroanatomi.
    Kozlova, Elena N.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Central nervous system stem/progenitor cells form neurons and peripheral glia after transplantation to the dorsal root ganglion.2006In: NeuroReport, ISSN 0959-4965, E-ISSN 1473-558X, Vol. 17, no 6, p. 623-628Article in journal (Refereed)
    Abstract [en]

    We asked whether neural stem/progenitor cells from the cerebral cortex of E14.5 enhanced green fluorescent protein transgenic mice are able to survive grafting and differentiate in the adult rat dorsal root ganglion. Neurospheres were placed in lumbar dorsal root ganglion cavities after removal of the dorsal root ganglia. Alternatively, dissociated neurospheres were injected into intact dorsal root ganglia. Enhanced green fluorescent protein-positive cells in the dorsal root ganglion cavity were located in clusters and expressed beta-III-tubulin or glial fibrillary acidic protein after 1 month, whereas after 3 months, surviving grafted cells expressed only glial fibrillary acidic protein. In the intact adult DRG, transplanted neural stem/progenitor cells surrounded dorsal root ganglion cells and fibers, and expressed glial but not neuronal markers. These findings show that central nervous system stem/progenitor cells can survive and differentiate into neurons and peripheral glia after xenotransplantation to the adult dorsal root ganglion.

  • 3.
    Dahlin, Joakim S
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Öhrvik, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Sandelin, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hallgren, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Lineage- CD34hi CD117int/hi FcϵRI+ cells in human blood constitute a rare population of mast cell progenitors2016In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 127, no 4, p. 383-391Article in journal (Refereed)
    Abstract [en]

    Mast cells are rare tissue-resident immune cells that are involved in allergic reactions, and their numbers are increased in the lungs of asthmatics. Murine lung mast cells arise from committed bone marrow-derived progenitors that enter the blood circulation, migrate through the pulmonary endothelium, and mature in the tissue. In humans, mast cells can be cultured from multipotent CD34(+) progenitor cells. However, a population of distinct precursor cells that give rise to mast cells has remained undiscovered. To our knowledge, this is the first report of human lineage(-) CD34(hi) CD117(int/hi) FcϵRI(+) progenitor cells, which represented only 0.0053% of the isolated blood cells in healthy individuals. These cells expressed integrin β7 and developed a mast cell-like phenotype, although with a slow cell division capacity in vitro. Isolated lineage(-) CD34(hi) CD117(int/hi) FcϵRI(+) blood cells had an immature mast cell-like appearance and expressed high levels of many mast cell-related genes as compared with human blood basophils in whole-transcriptome microarray analyses. Furthermore, serglycin, tryptase, and carboxypeptidase A mRNA transcripts were detected by quantitative RT-PCR. Altogether, we propose that the lineage(-) CD34(hi) CD117(int/hi) FcϵRI(+) blood cells are closely related to human tissue mast cells and likely constitute an immediate precursor population, which can give rise to predominantly mast cells. Furthermore, asthmatics with reduced lung function had a higher frequency of lineage(-) CD34(hi) CD117(int/hi) FcϵRI(+) blood mast cell progenitors than asthmatics with normal lung function.

  • 4.
    Ekman, Simon
    et al.
    Karolinska Univ Hosp, Oncol, Stockholm, Sweden.
    Sorensen, Jens Benn
    Rigshosp Blegdamsvej, Copenhagen O, Denmark.
    Rockberg, Julia
    Pygargus Ab, Ims Hlth Sweden, Rwes, Solna, Sweden.
    Sandelin, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Daumont, Melinda
    Bristol Myers Squibb, Rueil Malmaison, France.
    Sobocki, Patrik
    Pygargus Ab, Ims Hlth Sweden, Rwes, Solna, Sweden.
    Klint, Peter
    Bristol Myers Squibb, Solna, Sweden.
    Huang, Han-Yao
    Bristol Myers Squibb, Pennington, NJ USA.
    Svard, Jenny
    Pygargus Ab, Ims Hlth Sweden, Rwes, Solna, Sweden.
    Chirita, Oana
    Bristol Myers Squibb, Uxbridge, Middx, England.
    Jorgensen, Leif
    Pygargus Ab, Ims Hlth Sweden, Rwes, Solna, Sweden.
    Planck, Maria
    Lund Univ, Oncol & Pathol, Lund, Sweden.
    Overall Survival and Intermediate Outcomes among Scandinavian Non-Small Cell Lung Cancer Patients: The SCAN-LEAF Study2017In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 12, no 1, p. S6391-S6391Article in journal (Other academic)
  • 5. George, Julie
    et al.
    Lim, Jing Shan
    Jang, Se Jin
    Cun, Yupeng
    Ozretic, Luka
    Kong, Gu
    Leenders, Frauke
    Lu, Xin
    Fernandez-Cuesta, Lynnette
    Bosco, Graziella
    Mueller, Christian
    Dahmen, Ilona
    Jahchan, Nadine S.
    Park, Kwon-Sik
    Yang, Dian
    Karnezis, Anthony N.
    Vaka, Dedeepya
    Torres, Angela
    Wang, Maia Segura
    Korbel, Jan O.
    Menon, Roopika
    Chun, Sung-Min
    Kim, Deokhoon
    Wilkerson, Matt
    Hayes, Neil
    Engelmann, David
    Puetzer, Brigitte
    Bos, Marc
    Michels, Sebastian
    Vlasic, Ignacija
    Seidel, Danila
    Pinther, Berit
    Schaub, Philipp
    Becker, Christian
    Altmueller, Janine
    Yokota, Jun
    Kohno, Takashi
    Iwakawa, Reika
    Tsuta, Koji
    Noguchi, Masayuki
    Muley, Thomas
    Hoffmann, Hans
    Schnabel, Philipp A.
    Petersen, Iver
    Chen, Yuan
    Soltermann, Alex
    Tischler, Verena
    Choi, Chang-min
    Kim, Yong-Hee
    Massion, Pierre P.
    Zou, Yong
    Jovanovic, Dragana
    Kontic, Milica
    Wright, Gavin M.
    Russell, Prudence A.
    Solomon, Benjamin
    Koch, Ina
    Lindner, Michael
    Muscarella, Lucia A.
    la Torre, Annamaria
    Field, John K.
    Jakopovic, Marko
    Knezevic, Jelena
    Castanos-Velez, Esmeralda
    Roz, Luca
    Pastorino, Ugo
    Brustugun, Odd-Terje
    Lund-Iversen, Marius
    Thunnissen, Erik
    Koehler, Jens
    Schuler, Martin
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Sandelin, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Sanchez-Cespedes, Montserrat
    Salvesen, Helga B.
    Achter, Viktor
    Lang, Ulrich
    Bogus, Magdalena
    Schneider, Peter M.
    Zander, Thomas
    Ansen, Sascha
    Hallek, Michael
    Wolf, Juergen
    Vingron, Martin
    Yatabe, Yasushi
    Travis, William D.
    Nuernberg, Peter
    Reinhardt, Christian
    Perner, Sven
    Heukamp, Lukas
    Buettner, Reinhard
    Haas, Stefan A.
    Brambilla, Elisabeth
    Peifer, Martin
    Sage, Julien
    Thomas, Roman K.
    Comprehensive genomic profiles of small cell lung cancer2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 524, no 7563, p. 47-U73Article in journal (Refereed)
    Abstract [en]

    We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Dex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.

  • 6.
    Grudén, Stefan
    et al.
    LIDDS AB, Uppsala, Sweden.
    Sandelin, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Rasanen, Veera
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Hedeland, Mikael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry. National Veterinary Institute (SVA), Department of Chemistry, Environment and Feed Hygiene, Uppsala, Sweden.
    Axén, Niklas
    LIDDS AB, Uppsala, Sweden.
    Jeansson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Antitumoral effect and reduced systemic toxicity in mice after intra-tumoral injection of an in vivo solidifying calcium sulfate formulation with docetaxel2017In: European journal of pharmaceutics and biopharmaceutics, ISSN 0939-6411, E-ISSN 1873-3441, Vol. 114, p. 186-193Article in journal (Refereed)
    Abstract [en]

    Background

    Docetaxel is a cytostatic agent approved for treatment of non-small cell lung cancer as well as other cancers. Although docetaxel is an effective cytostatic agent, its effectiveness in clinical practice is associated with a variety of acute and long term side-effects. To overcome systemic side-effects, a slow release formulation based on calcium sulfate with docetaxel for intra-tumoral administration was developed.

    Methods

    Two formulations with the calcium sulfate NanoZolid technology were generated with a twofold difference in docetaxel drug load. The formulations were injected intra-tumorally as a paste which solidified within the tumor. The effects of the two intra-tumoral injection formulations were tested in female mice (n = 60) inoculated with subcutaneous Lewis lung carcinoma cells. The two formulations were compared to systemic intraperitoneal injection of docetaxel and a placebo formulation without docetaxel. Tumor volumes were measured and systemic side-effects were evaluated using body weight and cell counts from whole blood as well as plasma concentrations.

    Results

    Both docetaxel formulations showed a significantly higher antitumor efficacy compared to placebo, which was comparable to that of systemic administration of docetaxel. Moreover, the intra-tumoral formulations with docetaxel showed reduced systemic toxicity compared to systemic treatment, including less weight loss and no decrease in blood cell counts.

    Conclusions

    The results suggest that intra-tumoral slow release calcium sulfate based formulations with docetaxel can be an alternative strategy as an efficient local antitumoral treatment with reduced systemic toxicity.

  • 7.
    Holgersson, Georg
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Sandelin, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Hoye, Even
    Bergström, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Research and Development, Gävleborg.
    Henriksson, Roger
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Nyman, Jan
    Helsing, Martin
    Friesland, Signe
    Brodin, Ola
    Holgersson, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Lamberg Lundström, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Ekberg, Lars
    Morth, Charlotte
    Blystad, Thomas
    Ewers, Sven-Borje
    Loden, Britta
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    The Value of Induction Chemotherapy for Survival in Patients with Non-small Cell Lung Cancer Treated with Radiotherapy2012In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 32, no 4, p. 1339-1346Article in journal (Refereed)
    Abstract [en]

    Aim: The aim of the present study was to retrospectively investigate the impact of induction chemotherapy on treatment outcome in patients treated with curatively intended radiotherapy for non-small cell lung cancer (NSCLC). Patients and Methods: Patients with a diagnosed NSCLC that have been subjected to curatively intended irradiation (>= 50 Gy) and treated in an oncology department in Sweden during the years 1990-2000 were included in the study. Operated patients and patients having received concomitant chemotherapy were excluded. The included patients were localised by a manual search of all the oncology departments' medical records and radiation charts. Results: Patients treated with induction chemotherapy (n=79) had a significantly better overall survival compared with patients treated with radiotherapy alone (p=0.0097) in a univariate Cox regression analysis. A platinum/taxane combination produced the greatest survival benefit; hazard ratio=0.49 (95% confidence interval=0.31 to 0.75). Conclusion: We found that patients treated with induction chemotherapy in addition to radiotherapy for NSCLC have a better overall survival than patients treated with radiotherapy alone and that the best results are achieved using a platinum/taxane combination.

  • 8.
    Holgersson, Georg
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Sandelin, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Hoye, Even
    Bergström, Stefan
    Henriksson, Roger
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Nyman, Jan
    Helsing, Martin
    Friesland, Signe
    Holgersson, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Lamberg, Kristina Lundström
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Birath, Elisabet
    Mörth, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Blystad, Thomas
    Ewers, Sven-Börje
    Löden, Britta
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Swedish lung cancer radiation study group: the prognostic value of anaemia, thrombocytosis and leukocytosis at time of diagnosis in patients with non-small cell lung cancer2012In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 29, no 5, p. 3176-3182Article in journal (Refereed)
    Abstract [en]

    There is a need to improve the prognostic and predictive indicators in non-small cell lung cancer (NSCLC). At present, the main focus is on genetic predictive markers while the prognostic value of the standard blood variables related to haematopoiesis has been subjected to relatively limited attention. To study the prognostic potential of haemoglobin (Hgb), platelet (Plt) and white blood cell (WBC) levels at time of diagnosis in NSCLC patients, 835 NSCLC patients, stage I-IV, who received radiotherapy with curative intention (> 50 Gy), were included in the study. WBC, Plt, Hgb, gender, age at diagnosis, stage, surgery and first-line chemotherapy were studied in relation to overall survival. For patients with Hgb < 110 g/L and Hgb a parts per thousand yen 110 g/L), the median survival was 11.2 and 14.5 months, respectively (p = 0.0032). For WBC > 9.0 x 10(9)/L and < 9.0 x 10(9)/L, the median survival was 11.6 and 15.4 months, respectively (p < 0.0001). For Plt > 350 x 10(9)/L and < 350 x 10(9)/L, the median survival was 11.2 and 14.9 months, respectively (p < 0.0001). The median survival in patients with pathological results in all three markers was half of that in patients with normal levels of all three markers (8.0 and 16.0 months, respectively (p < 0.0001). The level of the three studied haematological biomarkers corresponds significantly to outcome in NSCLC. These results indicate that standard haematological variables may be used as guidance for the clinician in the decision-making regarding treatment intensity and patient information.

  • 9.
    Horie, Masafumi
    et al.
    Univ Tokyo, Grad Sch Med, Dept Resp Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan;Univ Tokyo, Div Hlth Serv Promot, Bunkyo Ku, 7-3-1 Hongo, Tokyo, Japan;RIKEN, Ctr Life Sci Technol, DGT, Tsurumi Ku, 1-7-22 Suehiro Cho, Yokohama, Kanagawa, Japan.
    Miyashita, Naoya
    Univ Tokyo, Grad Sch Med, Dept Resp Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.
    Mattsson, Johanna Sofia Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Mikami, Yu
    Univ Tokyo, Grad Sch Med, Dept Resp Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.
    Sandelin, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Brunnstrom, Hans
    Lund Univ, Dept Clin Sci Lund, Lab Med Reg Skane, Pathol, Lund, Sweden.
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Nagase, Takahide
    Univ Tokyo, Grad Sch Med, Dept Resp Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.
    Saito, Akira
    Univ Tokyo, Grad Sch Med, Dept Resp Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan;Univ Tokyo, Div Hlth Serv Promot, Bunkyo Ku, 7-3-1 Hongo, Tokyo, Japan.
    An integrative transcriptome analysis reveals a functional role for thyroid transcription factor-1 in small cell lung cancer2018In: Journal of Pathology, ISSN 0022-3417, E-ISSN 1096-9896, Vol. 246, no 2, p. 154-165Article in journal (Refereed)
    Abstract [en]

    Small cell lung cancer (SCLC) is a neuroendocrine tumour that exhibits rapid growth and metastatic spread. Although SCLC represents a prototypically undifferentiated cancer type, thyroid transcription factor-1 (TTF-1, gene symbol NKX2-1), a master regulator for pulmonary epithelial cell differentiation and lung morphogenesis, is strongly upregulated in this aggressive cancer type. The aim of this study was to evaluate a functional role for TTF-1 in SCLC. We demonstrated that achaete-scute complex homolog 1 (ASCL1), an essential transcription factor for neuroendocrine differentiation, positively regulated TTF-1 in SCLC cell lines. Subsequently, we described genes and microRNAs (miRNAs) that were possibly controlled by TTF-1 and identified nuclear factor IB (NFIB), a recently characterised driver of SCLC progression, as a transcriptional target of TTF-1. Our findings shine light on a regulatory axis in SCLC consisting of ASCL1/TTF-1/NFIB that potentially contributes to the tumourigenesis of SCLC.

  • 10.
    Isaksson, Johan
    et al.
    Gavle Cent Hosp, Dept Resp Med, Gavle, Sweden.
    Willen, Linda
    Gavle Cent Hosp, Dept Oncol, Gavle, Sweden.
    La Fleur, Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Mindus, Stephanie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Sundström, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Branden, Eva
    Gavle Cent Hosp, Dept Resp Med, Gavle, Sweden.
    Koyi, Hirsh
    Gavle Cent Hosp, Dept Resp Med, Gavle, Sweden.
    Sandelin, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Lamberg, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Moens, Lotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Lundberg, Gabriel
    Falun Cty Hosp, Dept Resp Med, Falun, Sweden.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Establishing Reflex NGS Testing in NSCLC in a Regional Network of County Hospitals in Central Sweden2017In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 12, no 1, p. S499-S500Article in journal (Other academic)
  • 11.
    La Fleur, Linnea
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Falk-Sörqvist, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Smeds, Patrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Sundström, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Mattsson, Johanna Sofia Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Brandén, Eva
    Gavle Cent Hosp, Dept Resp Med, Gavle, Sweden.
    Koyi, Hirsh
    Gavle Cent Hosp, Dept Resp Med, Gavle, Sweden.
    Isaksson, Johan
    Gavle Cent Hosp, Dept Resp Med, Gavle, Sweden.
    Brunnström, Hans
    Reg Labs Reg Skane, Pathol, Lund, Sweden.
    Sandelin, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Lamberg, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Landelius, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Nilsson, Mats
    Stockholm Univ, Dept Biochem & Biophys, Stockholm, Sweden.
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Moens, Lotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Mutation Profiling by Targeted Next Generation Sequencing of an Unselected NSCLC Cohort2017In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 12, no 1, p. S526-S527Article in journal (Other academic)
  • 12.
    La Fleur, Linnea
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Moens, Lotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Falk-Sörqvist, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Sundström, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Mattsson, Johanna S. M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Koyi, Hirsh
    Gavle Cent Hosp, Dept Resp Med, S-80187 Gavle, Sweden..
    Branden, Eva
    Gavle Cent Hosp, Dept Resp Med, S-80187 Gavle, Sweden..
    Brunnström, Hans
    Lund Univ, Div Oncol & Pathol, Dept Clin Sci Lund, Lund, Sweden..
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Sandelin, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Isaksson, Johan
    Gavle Cent Hosp, Dept Resp Med, S-80187 Gavle, Sweden..
    Jirström, Karin
    Lund Univ, Div Oncol & Pathol, Dept Clin Sci Lund, Lund, Sweden..
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Nilsson, Mats
    Stockholm Univ, Dept Biochem & Biophys, S-10691 Stockholm, Sweden..
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Mutation Profiling by Targeted Next-Generation Sequencing for Diagnostics and Patient Cohort Screening in FFPE NSCLC Samples2015In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 10, no 9, p. S697-S697Article in journal (Other academic)
  • 13.
    Paivandy, Aida
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Sandelin, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Igelström, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotherapy.
    Landelius, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Melo, Fabio R.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Pejler, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Induction of Human Lung Mast Cell Apoptosis by Granule Permeabilization: A Novel Approach for Targeting Mast Cells2017In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 8, article id 1645Article in journal (Refereed)
    Abstract [en]

    Mast cells are implicated as detrimental players in inflammatory lung diseases, particularly asthma. Mast cells respond to activating stimuli by releasing a wide panel of pro-inflammatory compounds that can contribute profoundly to the pathology, and there is currently an unmet need for strategies that efficiently ameliorate harmful effects of mast cells under such conditions. Here, we sought to evaluate a novel concept for targeting human lung mast cells, by assessing the possibility of selectively depleting the lung mast cells by induction of apoptosis. For this purpose, we used lysosomotropic agents, i.e., compounds that are known to permeabilize the secretory granules of mast cells, thereby releasing the contents of the granules into the cytosol. Either intact human lung tissue, purified human lung mast cells or mixed populations of human lung cells were incubated with the lysosomotropic agents mefloquine or siramesine, followed by measurement of apoptosis, reactive oxygen species (ROS) production, and release of cytokines. We show that human lung mast cells were highly susceptible to apoptosis induced by this strategy, whereas other cell populations of the lung were largely refractory. Moreover, we demonstrate that apoptosis induced by this mode is dependent on the production of ROS and that the treatment of lung tissue with lysosomotropic agents causes a decrease in the release of pathogenic cytokines. We conclude that selective apoptosis of human lung mast cells can be accomplished by administration of lysosomotropic agents, thus introducing the possibility of using such drugs as novel therapeutics in the treatment of inflammatory lung disorders such as asthma.

  • 14.
    Sandelin, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Prognosis, Prediction and Risk Assessment in the Prevention and Treatment of Non-Small Cell Lung Cancer2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Lung cancer causes more deaths than any other cancer. Smoking causes roughly 90% of lung cancer cases. Concurrent chemoradiation therapy is the standard of care for stage IIIb patients with performance status (PS) 0-1. A less toxic approach is warranted for less fit patients. To optimize care, the understanding of common clinical variables such as haematological responses to inflammation could be much improved. Adherence to guidelines for proper clinical work-up is vital to ensure patients’ optimal care, especially for predictive assays. Screening of high-risk patients is now being implemented internationally. Chronic pulmonary obstructive disease (COPD) patients, a group at high risk to develop lung cancer, could be of interest for screening.

    Methods: Patient cohorts collected nationally and regionally by manual search in patient records or automated search in electronic patient records and national registries were analysed in relation to overall survival, comorbidities, medication, treatment, smoking status, biomarkers and adherence to guidelines. Standard statistics were applied to adjust for confounding factors.

    Results: Induction chemotherapy results in longer overall survival than radiotherapy alone (15.6 and 11.6 months respectively). The overall survival for patients with combined anaemia, leucocytosis and thrombocytosis at diagnosis is half of what could be anticipated if blood samples are normal (8.0 and 16.0 months respectively). Fifty percent of patients were overlooked in the routine work-up with EGFR analysis. Less than 40% of the patients received EGFR-tyrosine kinase inhibitors in first-line therapy. The frequency of EGFR mutation was 9.9%. COPD patients with asthma and medicating with inhaled corticosteroids, specific serotonin reuptake inhibitors (SSRI) or beta-blockers have a significantly decreased risk of lung cancer.

    Conclusions: Patients unfit to receive chemoradiation therapy should be considered for induction chemotherapy sequentially to radiotherapy. A patient that presents with pathological blood samples is likely to have poor prognosis and diagnostic work-up should be thorough to optimize outcome. Inadequate adherence to the national guidelines regarding treatment and EGFR analysis was shown. COPD patients medicating with ICS, beta-blockers or SSRI and with a concurrent asthma diagnosis have a decreased risk of lung cancer. 

    List of papers
    1. The Value of Induction Chemotherapy for Survival in Patients with Non-small Cell Lung Cancer Treated with Radiotherapy
    Open this publication in new window or tab >>The Value of Induction Chemotherapy for Survival in Patients with Non-small Cell Lung Cancer Treated with Radiotherapy
    Show others...
    2012 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 32, no 4, p. 1339-1346Article in journal (Refereed) Published
    Abstract [en]

    Aim: The aim of the present study was to retrospectively investigate the impact of induction chemotherapy on treatment outcome in patients treated with curatively intended radiotherapy for non-small cell lung cancer (NSCLC). Patients and Methods: Patients with a diagnosed NSCLC that have been subjected to curatively intended irradiation (>= 50 Gy) and treated in an oncology department in Sweden during the years 1990-2000 were included in the study. Operated patients and patients having received concomitant chemotherapy were excluded. The included patients were localised by a manual search of all the oncology departments' medical records and radiation charts. Results: Patients treated with induction chemotherapy (n=79) had a significantly better overall survival compared with patients treated with radiotherapy alone (p=0.0097) in a univariate Cox regression analysis. A platinum/taxane combination produced the greatest survival benefit; hazard ratio=0.49 (95% confidence interval=0.31 to 0.75). Conclusion: We found that patients treated with induction chemotherapy in addition to radiotherapy for NSCLC have a better overall survival than patients treated with radiotherapy alone and that the best results are achieved using a platinum/taxane combination.

    Keywords
    NSCLC, lung cancer, radiotherapy, predictive value, age
    National Category
    Respiratory Medicine and Allergy Cancer and Oncology
    Identifiers
    urn:nbn:se:uu:diva-173639 (URN)000302492600028 ()
    Available from: 2012-05-09 Created: 2012-05-02 Last updated: 2017-12-07Bibliographically approved
    2. Swedish lung cancer radiation study group: the prognostic value of anaemia, thrombocytosis and leukocytosis at time of diagnosis in patients with non-small cell lung cancer
    Open this publication in new window or tab >>Swedish lung cancer radiation study group: the prognostic value of anaemia, thrombocytosis and leukocytosis at time of diagnosis in patients with non-small cell lung cancer
    Show others...
    2012 (English)In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 29, no 5, p. 3176-3182Article in journal (Refereed) Published
    Abstract [en]

    There is a need to improve the prognostic and predictive indicators in non-small cell lung cancer (NSCLC). At present, the main focus is on genetic predictive markers while the prognostic value of the standard blood variables related to haematopoiesis has been subjected to relatively limited attention. To study the prognostic potential of haemoglobin (Hgb), platelet (Plt) and white blood cell (WBC) levels at time of diagnosis in NSCLC patients, 835 NSCLC patients, stage I-IV, who received radiotherapy with curative intention (> 50 Gy), were included in the study. WBC, Plt, Hgb, gender, age at diagnosis, stage, surgery and first-line chemotherapy were studied in relation to overall survival. For patients with Hgb < 110 g/L and Hgb a parts per thousand yen 110 g/L), the median survival was 11.2 and 14.5 months, respectively (p = 0.0032). For WBC > 9.0 x 10(9)/L and < 9.0 x 10(9)/L, the median survival was 11.6 and 15.4 months, respectively (p < 0.0001). For Plt > 350 x 10(9)/L and < 350 x 10(9)/L, the median survival was 11.2 and 14.9 months, respectively (p < 0.0001). The median survival in patients with pathological results in all three markers was half of that in patients with normal levels of all three markers (8.0 and 16.0 months, respectively (p < 0.0001). The level of the three studied haematological biomarkers corresponds significantly to outcome in NSCLC. These results indicate that standard haematological variables may be used as guidance for the clinician in the decision-making regarding treatment intensity and patient information.

    Keywords
    Non-small cell lung cancer, Prognosis, Biomarker, Anaemia, Thrombocytosis, Leukocytosis
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-189133 (URN)10.1007/s12032-012-0247-3 (DOI)000311513800027 ()
    Available from: 2013-01-04 Created: 2012-12-25 Last updated: 2017-12-06Bibliographically approved
    3. Patients with Non-small Cell Lung Cancer Analyzed for EGFR: Adherence to Guidelines, Prevalence and Outcome
    Open this publication in new window or tab >>Patients with Non-small Cell Lung Cancer Analyzed for EGFR: Adherence to Guidelines, Prevalence and Outcome
    Show others...
    2015 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 35, no 7, p. 3979-3985Article in journal (Refereed) Published
    Abstract [en]

    Background: Epidermal growth factor receptor (EGFR) analysis is the first molecular test introduced in the routine care of patients with non-small cell lung cancer (NSCLC). In the present study, we describe the prevalence of EGFR mutations and the adherence to testing and treatment guidelines in a population-based Swedish NSCLC cohort. Materials and Methods: Patients with NSCLC analyzed for EGFR mutations were identified and their characteristics and survival data were retrieved. We compared the study cohort to a matched lung cancer population. Results: The EGFR mutation frequency was 10%. Mutations were enriched in women and in adenocarcinoma cases. Out of patients with advanced-stage NSCLC with non-squamous histology, only 49% were referred for EGFR analysis. Out of the patients with EGFR mutation and advanced disease, only 38% received EGFR-tyrosine kinase inhibitor (TKI) in first-line therapy. Conclusion: The EGFR-mutated NSCLC population studied is similar to other Western populations. Surprisingly, a large proportion of patients were not referred for EGFR analysis. Out of the patients with EGFR mutation, fewer than 40% received EGFR-TKI as first-line treatment. Our results highlight the need for follow-up of treatment and diagnostic algorithms in routine healthcare.

    Keywords
    Non-small cell lung cancer, EGFR, mutation, outcome, population, prevalence
    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:uu:diva-259096 (URN)000357116400029 ()26124345 (PubMedID)
    Available from: 2015-07-28 Created: 2015-07-27 Last updated: 2018-02-01Bibliographically approved
    4. Factors Associated With Risk Alteration Of Lung Cancer Development In Chronic Obstructive Pulmonary Disease Patients
    Open this publication in new window or tab >>Factors Associated With Risk Alteration Of Lung Cancer Development In Chronic Obstructive Pulmonary Disease Patients
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Keywords
    COPD, lung cancer, risk, epidemiology, comorbidity, ICS
    National Category
    Respiratory Medicine and Allergy
    Research subject
    Lung Medicine; Oncology
    Identifiers
    urn:nbn:se:uu:diva-261552 (URN)
    Available from: 2015-09-01 Created: 2015-09-01 Last updated: 2015-11-10
  • 15.
    Sandelin, Martin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Berglund, Anders
    Sundström, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    EGFR-Mutations and Resulting Treatment in a Nsclc Population-Based Cohort in Central Sweden2013In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 8, no S2, p. S904-S905Article in journal (Other academic)
  • 16.
    Sandelin, Martin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Berglund, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Sundström, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Bergqvist, Michael
    Bergstrom, Stefan
    Koyi, Hirsh
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Brandén, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Patients with Non-small Cell Lung Cancer Analyzed for EGFR: Adherence to Guidelines, Prevalence and Outcome2015In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 35, no 7, p. 3979-3985Article in journal (Refereed)
    Abstract [en]

    Background: Epidermal growth factor receptor (EGFR) analysis is the first molecular test introduced in the routine care of patients with non-small cell lung cancer (NSCLC). In the present study, we describe the prevalence of EGFR mutations and the adherence to testing and treatment guidelines in a population-based Swedish NSCLC cohort. Materials and Methods: Patients with NSCLC analyzed for EGFR mutations were identified and their characteristics and survival data were retrieved. We compared the study cohort to a matched lung cancer population. Results: The EGFR mutation frequency was 10%. Mutations were enriched in women and in adenocarcinoma cases. Out of patients with advanced-stage NSCLC with non-squamous histology, only 49% were referred for EGFR analysis. Out of the patients with EGFR mutation and advanced disease, only 38% received EGFR-tyrosine kinase inhibitor (TKI) in first-line therapy. Conclusion: The EGFR-mutated NSCLC population studied is similar to other Western populations. Surprisingly, a large proportion of patients were not referred for EGFR analysis. Out of the patients with EGFR mutation, fewer than 40% received EGFR-TKI as first-line treatment. Our results highlight the need for follow-up of treatment and diagnostic algorithms in routine healthcare.

  • 17.
    Sandelin, Martin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Akad Sjukhuset, Dept Immunol Genet & Pathol, Uppsala, Sweden..
    Gruden, S.
    LIDDS AB, Uppsala, Sweden..
    Räsänen, Veera
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Akad Sjukhuset, Dept Immunol Genet & Pathol, Uppsala, Sweden..
    Hedeland, M.
    Natl Vet Inst SVA, Dept Chem Environm & Feed Hyg, Uppsala, Sweden..
    Axen, N.
    LIDDS AB, Uppsala, Sweden..
    Jeansson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology. Akad Sjukhuset, Dept Immunol Genet & Pathol, Uppsala, Sweden..
    Antitumoral effect and reduced systemic toxicity in mice after intra-tumoral injection of an in vivo solidifying calcium sulfate formulation with docetaxel2017In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 28, no S2, article id 40PArticle in journal (Other academic)
  • 18.
    Sandelin, Martin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Mindus, Stephanie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Thuresson, Marcus
    Statisticon AB, Uppsala, Sweden.
    Lisspers, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Ställberg, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Johansson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Larsson, Kjell
    Karolinska Inst, Natl Inst Environm Med, Lung & Allergy Res Unit, Stockholm, Sweden.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Factors associated with lung cancer in COPD patients2018In: The International Journal of Chronic Obstructive Pulmonary Disease, ISSN 1176-9106, E-ISSN 1178-2005, Vol. 13, p. 1833-1839Article in journal (Refereed)
    Abstract [en]

    Background: The risk of dying of lung cancer is up to eightfold higher in patients with COPD than in age- and gender-matched controls. The aim of this study was to investigate the factors associated with lung cancer in a large cohort of COPD patients from primary care centers.

    Methods: To analyze whether age, gender, socioeconomic factors, comorbidity, and medication affect the risk of lung cancer in COPD, we used a COPD cohort of primary care patients. Data from primary care medical records and mandatory Swedish national registers were collected and linked in this population-based, retrospective observational registry study (NCT01146392).

    Results: Of the total cohort, 19,894 patients were included in the study. Five hundred and ninety-four lung cancer cases were diagnosed, corresponding to 3.0% of the studied population. In a multivariate analysis, the risk of lung cancer was lower if the COPD patients had a concurrent asthma diagnosis (HR: 0.54, CI: 0.41-0.71), while the risk of lung cancer increased with increasing age. A decreased lung cancer risk was observed in an exposure-dependent manner in patients who were prescribed inhaled corticosteroids (HR: 0.52, CI: 0.37-0.73), while the opposite was found for the use of acetylsalicylic acid (HR: 1.58, CI: 1.15-2.16).

    Conclusion: In this large population-based cohort, a concurrent asthma diagnosis and use of inhaled corticosteroids were independently related to decreased risk of lung cancer in COPD patients, while the use of acetylsalicylic acid was associated with an increased risk. The findings of the present study should be seen as hypothesis generating and need to be confirmed in prospective studies.

  • 19.
    Sandelin, Martin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Mindus, Stephanié
    Thuresson, Marcus
    Lisspers, Karin
    Ställberg, Björn
    Stratelis, Georgios
    Johanson, Gunnar
    Telg, Gunilla
    Goike, Helena
    Larsson, Kjell
    Janson, Christer
    Factors Associated With Risk Alteration Of Lung Cancer Development In Chronic Obstructive Pulmonary Disease PatientsManuscript (preprint) (Other academic)
  • 20.
    Sandelin, Martin
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Zabihi, Sheller
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Liu, Li
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Wicher, Grzegorz
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Kozlova, Elena
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Metastasis-associated S100A4 (Mts1) protein is expressed in subpopulations of sensory and autonomic neurons and in Schwann cells of the adult rat.2004In: J Comp Neurol., Vol. 473, no 2, p. 233-43Article in journal (Other (popular scientific, debate etc.))
    Abstract [en]

    S100A4 (Mts1) is a member of a family of calcium-binding proteins of the EF-hand type, which are widely expressed in the nervous system, where they appear to be involved in the regulation of neuron survival, plasticity, and response to injury or disease. S100A4 has previously been demonstrated in astrocytes of the white matter and rostral migratory stream of the adult rat. After injury, S100A4 is markedly up-regulated in affected central nervous white matter areas as well as in the periventricular area and rostral migratory stream. Here, we show that S100A4 is expressed in a subpopulation of dorsal root, trigeminal, geniculate, and nodose ganglion cells; in a subpopulation of postganglionic sympathetic and parasympathetic neurons; in chromaffin cells of the adrenal medulla; and in satellite and Schwann cells. In dorsal root ganglia, S100A4-positive cells appear to constitute a subpopulation of small ganglion neurons, a few of which coexpressed calcitonin gene-related peptide (CGRP) and Griffonia simplicifolia agglutinin (GSA) isolectin B4 (B4). S100A4 protein appears to be transported from dorsal root ganglia to the spinal cord, where it is deposited in the tract of Lissauer. After peripheral nerve or dorsal root injury, a few S100A4-positive cells coexpress CGRP, GSA, or galanin. Peripheral nerve or dorsal root injury induces a marked up-regulation of S100A4 expression in satellite cells in the ganglion and in Schwann cells at the injury site and in the distal stump. This pattern of distribution partially overlaps that of the previously studied S100B and S100A6 proteins, indicating a possible functional cooperation between these proteins. The presence of S100A4 in sensory neurons, including their processes in the central nervous system, suggests that S100A4 is involved in propagation of sensory impulses in specific fiber types. J. Comp. Neurol. 473:233-243, 2004. © 2004 Wiley-Liss, Inc.

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