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  • 1.
    Birgisson, H
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Talbäck, M
    Gunnarsson, U
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Påhlman, L
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Glimelius, B
    Department of Oncology, Radiology and Clinical Immunology.
    Improved survival in cancer of the colon and rectum in Sweden.2005In: Eur J Surg Oncol, ISSN 0748-7983, Vol. 31, no 8, p. 845-53Article in journal (Refereed)
  • 2.
    Birgisson, Helgi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Edlund, Karolina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Wallin, Ulrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Kultima, Hanna Göransson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mayrhofer, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Isaksson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Sundström, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Microsatellite instability and mutations in BRAF and KRAS are significant predictors of disseminated disease in colon cancer2015In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 15, article id 125Article in journal (Refereed)
    Abstract [en]

    Background: Molecular alterations are well studied in colon cancer, however there is still need for an improved understanding of their prognostic impact. This study aims to characterize colon cancer with regard to KRAS, BRAF, and PIK3CA mutations, microsatellite instability (MSI), and average DNA copy number, in connection with tumour dissemination and recurrence in patients with colon cancer. Methods: Disease stage II-IV colon cancer patients (n = 121) were selected. KRAS, BRAF, and PIK3CA mutation status was assessed by pyrosequencing and MSI was determined by analysis of mononucleotide repeat markers. Genome-wide average DNA copy number and allelic imbalance was evaluated by SNP array analysis. Results: Patients with mutated KRAS were more likely to experience disease dissemination (OR 2.75; 95% CI 1.28-6.04), whereas the opposite was observed for patients with BRAF mutation (OR 0.34; 95% 0.14-0.81) or MSI (OR 0.24; 95% 0.09-0.64). Also in the subset of patients with stage II-III disease, both MSI (OR 0.29; 95% 0.10-0.86) and BRAF mutation (OR 0.32; 95% 0.16-0.91) were related to lower risk of distant recurrence. However, average DNA copy number and PIK3CA mutations were not associated with disease dissemination. Conclusions: The present study revealed that tumour dissemination is less likely to occur in colon cancer patients with MSI and BRAF mutation, whereas the presence of a KRAS mutation increases the likelihood of disseminated disease.

  • 3.
    Birgisson, Helgi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Jirström, Karin
    Stenman, Ulf-Håkan
    Serum concentrations of human chorionic gonadotropin beta and its association with survival in patients with colorectal cancer2012In: CANCER BIOMARK, ISSN 1574-0153, Vol. 11, no 4, p. 173-181Article in journal (Refereed)
    Abstract [en]

    Increased serum concentrations of the beta subunit of human chorionic gonadotropin (hCG beta) are associated with adverse prognosis in several cancers. The aim of the present study was to analyse the association between serum hCG beta recurrence, and survival, in patients with colorectal cancer. The concentrations of hCG beta were determined in serum collected preoperatively from 324 patients with colorectal cancer, of whom 270 were curatively treated. The serum concentrations of hCG beta were associated with increasing age and they were higher in women than in men. Using the 75th percentile (1.55 pmol/L) as a cut-off for serum hCG beta, overall survival (OS) was shorter in patients with elevated concentrations (HR 1.95; 95% CI 1.39-2.74; P = 0.004), and this association was stronger in women (P = 0.022) than in men (P = 0.061). In multivariate analyses including age, disease stage, tumour differentiation, vascular invasion and CEA, high serum hCG beta concentrations remained an independent prognostic factor for adverse OS in women (HR 2.26; 95% CI 1.39-3.67), but not in men (HR 0.78; 95% CI 0.41-1.51). The same trend was observed for disease free-and cancer specific survival. High serum concentration of hCG beta is an independent prognostic factor for adverse outcome in women with colorectal cancer.

  • 4.
    Birgisson, Helgi
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Moller, PH
    Birgisson, S
    Thoroddsen, A
    Asgeirsson, KS
    Sigurjonsson, SV
    Magnusson, J
    Acute pancreatitis: a prospective study of its incidence, aetiology, severity and mortality in Iceland.2002In: Eur J Surg, Vol. 168, no 5, p. 278-82Article in journal (Refereed)
  • 5.
    Birgisson, Helgi
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Pahlman, Lars
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Gunnarsson, Ulf
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Glimelius, Bengt
    Adverse effects of preoperative radiation therapy for rectal cancer: long-term follow-up of the Swedish Rectal Cancer Trial.2005In: J Clin Oncol, ISSN 0732-183X, Vol. 23, no 34, p. 8697-705Article in journal (Refereed)
  • 6.
    Birgisson, Helgi
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Pahlman, Lars
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Gunnarsson, Ulf
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Glimelius, Bengt
    Occurrence of second cancers in patients treated with radiotherapy for rectal cancer.2005In: J Clin Oncol, ISSN 0732-183X, Vol. 23, no 25, p. 6126-31Article in journal (Refereed)
  • 7.
    Birgisson, Helgi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Wallin, Ulrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Survival endpoints in colorectal cancer and the effect of second primary other cancer on disease free survival2011In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 11, p. 438-Article in journal (Refereed)
    Abstract [en]

    Background: In cancer research the selection and definitions of survival endpoints are important and yet they are not used consistently. The aim of this study was to compare different survival endpoints in patients with primary colorectal cancer (CRC) and to understand the effect of second primary other cancer on disease-free survival (DFS) calculations.

    Methods: A population-based cohort of 415 patients with CRC, 332 of whom were treated with curative intention between the years 2000-2003, was analysed. Events such as locoregional recurrence, distant metastases, second primary cancers, death, cause of death and loss to follow-up were recorded. Different survival endpoints, including DFS, overall survival, cancer-specific survival, relapse-free survival, time to treatment failure and time to recurrence were compared and DFS was calculated with and without inclusion of second primary other cancers.

    Results: The events that occurred most often in patients treated with curative intention were non-cancer-related death (n = 74), distant metastases (n = 66) and death from CRC (n = 59). DFS was the survival endpoint with most events (n = 170) followed by overall survival (n = 144) and relapse-free survival (n = 139). Fewer events were seen for time to treatment failure (n = 80), time to recurrence (n = 68) and cancer-specific survival (n = 59). Second primary other cancer occurred in 26 patients and its inclusion as an event in DFS calculations had a detrimental effect on the survival. The DFS for patients with stage I-III disease was 62% after 5 years if second primary other cancer was not included as an event, compared with 58% if it was. However, the difference was larger for stage II (68 vs 60%) than for stage III (49 vs 47%).

    Conclusions: The inclusion of second primary other cancer as an endpoint in DFS analyses significantly alters the DFS for patients with CRC. Researchers and journals must clearly define survival endpoints in all trial protocols and published manuscripts.

  • 8.
    Enblad, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Birgisson, H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Ekbom, Anders
    Department of Medicine, Clinical Epidemiology Unit, Karolinska institutet.
    Sandin, Fredrik
    Regional Cancer Centre, Uppsala University Hospital.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Increased incidence of bowel cancer after non-surgical treatment of appendicitis2017In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 43, no 11, p. 2067-2075Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: There is an ongoing debate on the use of antibiotics instead of appendectomy for treating appendicitis but diagnostic difficulties and longstanding inflammation might lead to increased incidence of bowel cancer in these patients. The aim of this population-based study was to investigate the incidence of bowel cancer after non-surgical treatment of appendicitis.

    PATIENTS AND METHODS: Patients diagnosed with appendicitis but lacking the surgical procedure code for appendix removal were retrieved from the Swedish National Inpatient Register 1987-2013. The cohort was matched with the Swedish Cancer Registry and the standardised incidence ratios (SIR) with 95% confidence interval (95% CI) for appendiceal, colorectal and small bowel cancers were calculated.

    RESULTS: Of 13 595 patients with non-surgical treatment of appendicitis, 352 (2.6%) were diagnosed with appendiceal, colorectal or small bowel cancer (SIR 4.1, 95% CI 3.7-4.6). The largest incidence increase was found for appendiceal (SIR 35, 95% CI 26-46) and right-sided colon cancer (SIR 7.5, 95% CI 6.6-8.6). SIR was still elevated when excluding patients with less than 12 months since appendicitis and the incidence of right-sided colon cancer was elevated five years after appendicitis (SIR 3.5, 95% CI 2.1-5.4). An increased incidence of bowel cancer was found after appendicitis with abscess (SIR 4.6, 95% CI 4.0-5.2), and without abscess (SIR 3.5, 95% CI 2.9-4.1).

    CONCLUSION: Patients with non-surgical treatment of appendicitis have an increased short and long-term incidence of bowel cancer. This should be considered in the discussion about optimal management of patients with appendicitis.

  • 9.
    Enblad, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Birgisson, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Wanders, Alkwin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Sköldberg, Filip
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Ghanipour, Lana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Importance of Absent Neoplastic Epithelium in Patients Treated With Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy2016In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 23, no 4, p. 1149-1156Article in journal (Refereed)
    Abstract [en]

    The importance of absent neoplastic epithelium in specimens from cytoreductive surgery (CRS) is unknown. This study aimed to investigate the prevalence and prognostic value of histopathology without neoplastic epithelium in patients treated with CRS and hyperthermic intraperitoneal chemotherapy (HIPEC). Data were extracted from medical records and histopathology reports for patients treated with initial CRS and HIPEC at Uppsala University Hospital, Sweden, between 2004 and 2012. Patients with inoperable disease and patients undergoing palliative non-CRS surgery were excluded from the study. Patients lacking neoplastic epithelium in surgical specimens from CRS, with or without mucin, were classified as "neoplastic epithelium absent" (NEA), and patients with neoplastic epithelium were classified as "neoplastic epithelium present" (NEP). The study observed NEA in 78 of 353 patients (22 %). Mucin was found in 28 of the patients with NEA. For low-grade appendiceal mucinous neoplasms and adenomas, the 5-year overall survival rate was 100 % for NEA and 84 % for NEP, and the 5-year recurrence-free survival rate was 100 % for NEA and 59 % for NEP. For appendiceal/colorectal adenocarcinomas (including tumors of the small intestine), the 5-year overall survival rate was 61 % for NEA and 38 % for NEP, and the 5-year recurrence-free survival rate was 60 % for NEA and 14 % for NEP. Carcinoembryonic antigen level, peritoneal cancer index, and completeness of the cytoreduction score were lower in patients with NEA. A substantial proportion of patients undergoing CRS and HIPEC have NEA. These patients have a favorable prognosis and a decreased risk of recurrence. Differences in patient selection can affect the proportion of NEA and hence explain differences in survival rates between reported series.

  • 10.
    Folkesson, Joakim
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Birgisson, Helgi
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Pahlman, Lars
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Cedermark, Bjorn
    Glimelius, Bengt
    Department of Oncology, Radiology and Clinical Immunology. ONK.
    Gunnarsson, Ulf
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Swedish Rectal Cancer Trial: long lasting benefits from radiotherapy on survival and local recurrence rate.2005In: J Clin Oncol, ISSN 0732-183X, Vol. 23, no 24, p. 5644-50Article in journal (Refereed)
  • 11.
    Ghanipour, Lana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Darmanis, Spyros
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Landegren, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Birgisson, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Detection of prognostic biomarkers with solid-phase proximity ligation assay in patients with colorectal cancer2016In: Translational Oncology, ISSN 1944-7124, E-ISSN 1936-5233, Vol. 9, no 3, p. 251-255Article in journal (Refereed)
    Abstract [en]

    Background: In the search for prognostic biomarkers a significant amount of precious biobanked blood samples is needed if conventional analyses are used. Solid-phase proximity ligation assay (SP-PLA) is an analytic method with the ability to analyse many proteins at the same time in small amounts of plasma. The aim of this study was to explore the potential use of  SP-PLA in patients with colorectal cancer (CRC).

    Material and methods: Plasma from patients with stage I-IV CRC, with (n=31) and without (n=29) disease dissemination at diagnosis or later, was analysed with SP-PLA using 35 antibodies targeting an equal number of proteins in 5 ml plasma. Carcinoembryonic antigen (CEA), analysed earlier on this cohort, was used as a reference.

    Results: A total of 21 of the 35 proteins were detectable with SP-PLA. Patients in stage II-III with disseminated disease had lower plasma concentrations of HCC-4 (p=0.025). Low plasma levels of TIMP-1 were seen in patients with disseminated disease stage II (p=0.003). The level of CEA was higher in patients with disease dissemination compared to those without (p=0.007).

    Conclusion: SP-PLA has the ability to analyse many tumour markers simultaneously in a small amount of blood. However, none of the markers selected for the present SP-PLA analyses gave better prognostic information compared with CEA. 

  • 12.
    Glimelius, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Melin, Beatrice
    Umeå Univ, Dept Radiat Sci, Umeå.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Beskow, Anna H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Birgisson, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Björ, Ove
    Umeå Univ, Dept Radiat Sci, Umeå.
    Edqvist, Per-Henrik D
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Hansson, Tony
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Helleday, Thomas
    Karolinska Inst, Div Translat Med & Chem Biol, Dept Med Biochem & Biophys, Sci Life Lab, Stockholm.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Henriksson, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Hesselager, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hultdin, Magnus
    Umeå Univ, Dept Med Biosci, Pathol, Umeå.
    Häggman, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Jonsson, Håkan
    Umeå Univ, Dept Radiat Sci, Umeå.
    Larsson, Chatarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Lindman, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Ljuslinder, Ingrid
    Umeå Univ, Dept Radiat Sci, Umeå.
    Mindus, Stephanie
    Akad Sjukhuset, Lung & Allergy Clin, Uppsala.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Ponten, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Riklund, Katrine
    Umeå Univ, Dept Radiat Sci, Umeå.
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Sandin, Fredrik
    Uppsala Univ Hosp, RCC Uppsala Örebro, Uppsala.
    Schwenk, Jochen M.
    KTH Royal Inst Technol, Sch Biotechnol, Affin Prote, SciLifeLab, Solna.
    Stenling, Roger
    Umeå Univ, Dept Med Biosci, Pathol, Umeå.
    Stålberg, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Thellenberg Karlsson, Camilla
    Umeå Univ, Dept Radiat Sci, Umeå.
    Westermark, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology.
    Bergh, Anders
    Umeå Univ, Dept Med Biosci, Pathol, Umeå.
    Claesson-Welsh, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Palmqvist, Richard
    Umeå Univ, Dept Med Biosci, Pathol, Umeå.
    Sjöblom, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    U-CAN: a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden.2018In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 2, p. 187-194Article in journal (Refereed)
    Abstract [en]

    Background: Progress in cancer biomarker discovery is dependent on access to high-quality biological materials and high-resolution clinical data from the same cases. To overcome current limitations, a systematic prospective longitudinal sampling of multidisciplinary clinical data, blood and tissue from cancer patients was therefore initiated in 2010 by Uppsala and Umeå Universities and involving their corresponding University Hospitals, which are referral centers for one third of the Swedish population.

    Material and Methods: Patients with cancer of selected types who are treated at one of the participating hospitals are eligible for inclusion. The healthcare-integrated sampling scheme encompasses clinical data, questionnaires, blood, fresh frozen and formalin-fixed paraffin-embedded tissue specimens, diagnostic slides and radiology bioimaging data.

    Results: In this ongoing effort, 12,265 patients with brain tumors, breast cancers, colorectal cancers, gynecological cancers, hematological malignancies, lung cancers, neuroendocrine tumors or prostate cancers have been included until the end of 2016. From the 6914 patients included during the first five years, 98% were sampled for blood at diagnosis, 83% had paraffin-embedded and 58% had fresh frozen tissues collected. For Uppsala County, 55% of all cancer patients were included in the cohort.

    Conclusions: Close collaboration between participating hospitals and universities enabled prospective, longitudinal biobanking of blood and tissues and collection of multidisciplinary clinical data from cancer patients in the U-CAN cohort. Here, we summarize the first five years of operations, present U-CAN as a highly valuable cohort that will contribute to enhanced cancer research and describe the procedures to access samples and data.

  • 13. Kodeda, K.
    et al.
    Johansson, R.
    Zar, N.
    Birgisson, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Dahlberg, M.
    Skullman, S.
    Lindmark, G.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Martling, A.
    Time trends, improvements and national auditing of rectal cancer management over an 18-year period2015In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 17, no 9, p. O168-O179Article in journal (Refereed)
    Abstract [en]

    Aim: The main aims were to explore time trends in the management and outcome of patients with rectal cancer in a national cohort and to evaluate the possible impact of national auditing on overall outcomes. A secondary aim was to provide population-based data for appraisal of external validity in selected patient series.

    Method: Data from the Swedish ColoRectal Cancer Registry with virtually complete national coverage were utilized in this cohort study on 29925 patients with rectal cancer diagnosed between 1995 and 2012. Of eligible patients, nine were excluded.

    Results: During the study period, overall, relative and disease-free survival increased. Postoperative mortality after 30 and 90days decreased to 1.7% and 2.9%. The 5-year local recurrence rate dropped to 5.0%. Resection margins improved, as did peri-operative blood loss despite more multivisceral resections being performed. Fewer patients underwent palliative resection and the proportion of non-operated patients increased. The proportions of temporary and permanent stoma formation increased. Preoperative radiotherapy and chemoradiotherapy became more common as did multidisciplinary team conferences. Variability in rectal cancer management between healthcare regions diminished over time when new aspects of patient care were audited.

    Conclusion: There have been substantial changes over time in the management of patients with rectal cancer, reflected in improved outcome. Much indirect evidence indicates that auditing matters, but without a control group it is not possible to draw firm conclusions regarding the possible impact of a quality control registry on faster shifts in time trends, decreased variability and improvements. Registry data were made available for reference.

  • 14. Larsson, Anna
    et al.
    Fridberg, Marie
    Gaber, Alexander
    Nodin, Björn
    Leveen, Per
    Jönsson, Göran
    Uhlen, Mathias
    Birgisson, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Jirström, Karin
    Validation of podocalyxin-like protein as a biomarker of poor prognosis in colorectal cancer2012In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 12, p. 282-Article in journal (Refereed)
    Abstract [en]

    Background: Podocalyxin-like 1 (PODXL) is a cell-adhesion glycoprotein and stem cell marker that has been associated with an aggressive tumour phenotype and adverse outcome in several cancer types. We recently demonstrated that overexpression of PODXL is an independent factor of poor prognosis in colorectal cancer (CRC). The aim of this study was to validate these results in two additional independent patient cohorts and to examine the correlation between PODXL mRNA and protein levels in a subset of tumours. Method: PODXL protein expression was analyzed by immunohistochemistry in tissue microarrays with tumour samples from a consecutive, retrospective cohort of 270 CRC patients (cohort 1) and a prospective cohort of 337 CRC patients (cohort 2). The expression of PODXL mRNA was measured by real-time quantitative PCR in a subgroup of 62 patients from cohort 2. Spearman's Rho and Chi-Square tests were used for analysis of correlations between PODXL expression and clinicopathological parameters. Kaplan Meier analysis and Cox proportional hazards modelling were applied to assess the relationship between PODXL expression and time to recurrence (TTR), disease free survival (DFS) and overall survival (OS). Results: High PODXL protein expression was significantly associated with unfavourable clinicopathological characteristics in both cohorts. In cohort 1, high PODXL expression was associated with a significantly shorter 5-year OS in both univariable (HR = 2.28; 95% CI 1.43-3.63, p = 0.001) and multivariable analysis (HR = 2.07; 95% CI 1.25-3.43, p = 0.005). In cohort 2, high PODXL expression was associated with a shorter TTR (HR = 2.93; 95% CI 1.26-6.82, p = 0.013) and DFS (HR = 2.44; 95% CI 1.32-4.54, p = 0.005), remaining significant in multivariable analysis, HR = 2.50; 95% CI 1.05-5.96, p = 0.038 for TTR and HR = 2.11; 95% CI 1.13-3.94, p = 0.019 for DFS. No significant correlation could be found between mRNA levels and protein expression of PODXL and there was no association between mRNA levels and clinicopathological parameters or survival. Conclusions: Here, we have validated the previously demonstrated association between immunohistochemical expression of PODXL and poor prognosis in CRC in two additional independent patient cohorts. The results further underline the potential utility of PODXL as a biomarker for more precise prognostication and treatment stratification of CRC patients.

  • 15.
    Larsson, Anna H.
    et al.
    Lund Univ, Dept Clin Sci, Div Oncol & Pathol, Lund, Sweden..
    Lehn, Sophie
    Lund Univ, Dept Clin Sci, Div Oncol & Pathol, Lund, Sweden..
    Wangefjord, Sakarias
    Lund Univ, Dept Clin Sci, Div Oncol & Pathol, Lund, Sweden..
    Karnevi, Emelie
    Lund Univ, Dept Clin Sci, Div Oncol & Pathol, Lund, Sweden..
    Kuteeva, Eugenia
    AlbaNova Univ Ctr, Atlas Antibodies AB, Stockholm, Sweden..
    Sundström, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Nodin, Björn
    Lund Univ, Dept Clin Sci, Div Oncol & Pathol, Lund, Sweden..
    Uhlen, Mathias
    KTH Royal Inst Technol, Sci Life Lab, Stockholm, Sweden..
    Eberhard, Jakob
    Lund Univ, Dept Clin Sci, Div Oncol & Pathol, Lund, Sweden..
    Birgisson, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Jirström, Karin
    Lund Univ, Dept Clin Sci, Div Oncol & Pathol, Lund, Sweden..
    Significant association and synergistic adverse prognostic effect of podocalyxin-like protein and epidermal growth factor receptor expression in colorectal cancer2016In: Journal of Translational Medicine, ISSN 1479-5876, E-ISSN 1479-5876, Vol. 14, article id 128Article in journal (Refereed)
    Abstract [en]

    Background: Podocalyxin-like 1 (PODXL) is an anti-adhesive transmembrane protein that has been demonstrated to be an independent factor of poor prognosis in colorectal cancer (CRC). The gene encoding PODXL is located to chromosome 7, which also harbours the gene for the epidermal growth factor receptor (EGFR). The aim of this study was to examine the associations between PODXL and EGFR expression in CRC in vitro and in vivo.

    Methods: EGFR expression was analysed in tumours from three independent patient cohorts; cohort 1 (n = 533), cohort 2 (n = 259) and cohort 3 (n = 310), previously analysed for immunohistochemical PODXL expression and KRAS and BRAF mutations (cohort 1 and 3). Levels of EGFR and PODXL were determined by western blot in six different CRC cell lines.

    Results: High expression of PODXL was significantly associated with high EGFR expression (p < 0.001) in all three cohorts, and with BRAF mutation (p < 0.001) in cohort 1 and 3. High EGFR expression correlated with BRAF mutation (p < 0.001) in cohort 1. High EGFR expression was associated with adverse clinicopathological factors and independently predicted a reduced 5-year overall survival (OS) in cohort 1 (HR 1.77; 95 % CI 1.27-2.46), cohort 2 (HR 1.58; 95 % CI 1.05-2.38) and cohort 3 (HR 1.83; 95 % CI 1.19-2.81). The highest risk of death within 5 years was observed in patients with tumours displaying high expression of both EGFR and PODXL in cohort 1 and 3 (HR 1.97; 95 % CI 1.18-3.28 and HR 3.56; 95 % CI 1.75-7.22, respectively). Western blot analysis showed a uniform expression of PODXL and EGFR in all six examined CRC cell lines.

    Conclusions: The results from this study demonstrate that high expression of EGFR is an independent factor of poor prognosis in CRC. Moreover, strong links have been uncovered between expression of the recently proposed biomarker candidate PODXL with EGFR expression in CRC in vivo and in vitro, and with BRAF mutation in vivo. High expression of both PODXL and EGFR may also have a synergistic adverse effect on survival. These findings suggest a potential functional link in CRC between PODXL, EGFR and BRAF, all originating from chromosome 7, which may be highly relevant in the clinical setting and therefore merit future in-depth study.

  • 16.
    Lomnytska, M.
    et al.
    Karolinska Inst, Womens & Childrens Hlth, Karolinska Univ Hosp, Obstet & Gynaecol, Stockholm, Sweden..
    Stalberg, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Akademiska Hosp, Uppsala, Sweden..
    Birgisson, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Akademiska Hosp, Uppsala, Sweden..
    Silins, Ilvars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Akademiska, Uppsala, Sweden..
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Akademiska Hosp, Uppsala, Sweden..
    Complications Related To Surgery For Ovarian Cancer With Intestinal Involvement2015In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 25, no 9, p. 492-492Article in journal (Other academic)
  • 17.
    Martling, A.
    et al.
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Smedby, K. E.
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden..
    Birgisson, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Olsson, H.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Granath, F.
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden..
    Ekbom, A.
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden..
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Risk of second primary cancer in patients treated with radiotherapy for rectal cancer2017In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 104, no 3, p. 278-287Article in journal (Refereed)
    Abstract [en]

    Background: Many patients with rectal cancer receive radiotherapy (RT) to reduce the risk of local recurrence. Radiation may give rise to adverse effects, including second primary cancers. In view of the divergent results of previous studies, the present study evaluated the risk of second primary cancer following RT in all randomized RT rectal cancer trials conducted in Sweden and in the Swedish ColoRectal Cancer Registry (SCRCR).

    Methods: Patients included in five randomized trials and the SCRCR were linked to the Swedish Cancer Registry. Cox regression models estimated the hazard ratio (HR) of second primary cancer among patients who received RT compared with those who did not.

    Results: A total of 13 457 patients were included in this study; 7024 (52.2 per cent) received RT and 6433 (47.8 per cent) had surgery alone. Overall, no increased risk of second primary cancer was observed with RT (HR 1.03; 95 per cent c. i. 0.92 to 1.15), independently of follow-up time and location within or outside of the irradiated volume. In the randomized trials, with longer follow-up (maximum 31 years), a slight increase was observed outside of (HR 1.33, 1.01 to 1.74) but not within (HR 1.11, 0.73 to 1.67) the irradiated volume. Irradiated men had a lower risk of prostate cancer than those treated with surgery alone (HR 068, 0.51 to 091).

    Conclusion: Overall, there was no increased risk of second primary cancer following RT for rectal cancer within or outside of the irradiated volume up to 20 years of follow-up. Men with rectal cancer who received RT had a reduced risk of prostate cancer.

  • 18.
    Mayrhofer, Markus
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Kultima, Hanna Göransson
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Birgisson, Helgi
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Sundström, Magnus
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Mathot, Lucy
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics.
    Edlund, Karolina
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Viklund, Björn
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Sjöblom, Tobias
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics.
    Botling, Johan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Micke, Patrick
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Påhlman, Lars
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Isaksson, Anders
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    1p36 deletion is a marker for tumour dissemination in microsatellite stable stage II-III colon cancer2014In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 14, p. 872-Article in journal (Refereed)
    Abstract [en]

    Background: The clinical behaviour of colon cancer is heterogeneous. Five-year overall survival is 50-65% with all stages included. Recurring somatic chromosomal alterations have been identified and some have shown potential as markers for dissemination of the tumour, which is responsible for most colon cancer deaths. We investigated 115 selected stage II-IV primary colon cancers for associations between chromosomal alterations and tumour dissemination. Methods: Follow-up was at least 5 years for stage II-III patients without distant recurrence. Affymetrix SNP 6.0 microarrays and allele-specific copy number analysis were used to identify chromosomal alterations. Fisher's exact test was used to associate alterations with tumour dissemination, detected at diagnosis (stage IV) or later as recurrent disease (stage II-III). Results: Loss of 1p36.11-21 was associated with tumour dissemination in microsatellite stable tumours of stage II-IV (odds ratio = 5.5). It was enriched to a similar extent in tumours with distant recurrence within stage II and stage III subgroups, and may therefore be used as a prognostic marker at diagnosis. Loss of 1p36.11-21 relative to average copy number of the genome showed similar prognostic value compared to absolute loss of copies. Therefore, the use of relative loss as a prognostic marker would benefit more patients by applying also to hyperploid cancer genomes. The association with tumour dissemination was supported by independent data from the The Cancer Genome Atlas. Conclusion: Deletions on 1p36 may be used to guide adjuvant treatment decisions in microsatellite stable colon cancer of stages II and III.

  • 19.
    Padhan, Narendra
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology. Uppsala University, Science for Life Laboratory, SciLifeLab. Rudbeck Lab, S-75185 Uppsala, Sweden..
    Yan, Junhong
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab. Rudbeck Lab, S-75185 Uppsala, Sweden.;Eindhoven Univ Technol, Inst Complex Mol Syst, Dept Biomed Engn, NL-5600 MB Eindhoven, Netherlands..
    Boge, Annegret
    Protein Simple, 3001 Orchard Pkwy, San Jose, CA 95134 USA..
    Scrivener, Elaine
    Protein Simple, 3001 Orchard Pkwy, San Jose, CA 95134 USA..
    Birgisson, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Zieba, Agata
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab. Rudbeck Lab, S-75185 Uppsala, Sweden..
    Gullberg, Mats
    Olink Biosci, Dag Hammarskjolds Vag 52B, S-75237 Uppsala, Sweden..
    Kamali-Moghaddam, Masood
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools. Uppsala University, Science for Life Laboratory, SciLifeLab. Rudbeck Lab, S-75185 Uppsala, Sweden..
    Claesson-Welsh, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology. Uppsala University, Science for Life Laboratory, SciLifeLab. Rudbeck Lab, S-75185 Uppsala, Sweden..
    Landegren, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools. Uppsala University, Science for Life Laboratory, SciLifeLab. Rudbeck Lab, S-75185 Uppsala, Sweden..
    Highly sensitive and specific protein detection via combined capillary isoelectric focusing and proximity ligation2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 1490Article in journal (Refereed)
    Abstract [en]

    Detection and quantification of proteins and their post-translational modifications are crucial to decipher functions of complex protein networks in cell biology and medicine. Capillary isoelectric focusing together with antibody-based detection can resolve and identify proteins and their isoforms with modest sample input. However, insufficient sensitivity prevents detection of proteins present at low concentrations and antibody cross-reactivity results in unspecific detection that cannot be distinguished from bona fide protein isoforms. By using DNA-conjugated antibodies enhanced signals can be obtained via rolling circle amplification (RCA). Both sensitivity and specificity can be greatly improved in assays dependent on target recognition by pairs of antibodies using in situ proximity ligation assays (PLA). Here we applied these DNA-assisted RCA techniques in capillary isoelectric focusing to resolve endogenous signaling transducers and isoforms along vascular endothelial growth factor (VEGF) signaling pathways at concentrations too low to be detected in standard assays. We also demonstrate background rejection and enhanced specificity when protein detection depended on binding by pairs of antibodies using in situ PLA, compared to assays where each antibody preparation was used on its own.

  • 20. Pena, Cristina
    et al.
    Virtudes Cespedes, Maria
    Lindh, Maja Bradic
    Kiflemariam, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics.
    Mezheyeuski, Artur
    Edqvist, Per-Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Hagglof, Christina
    Birgisson, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Bojmar, Linda
    Jirstrom, Karin
    Sandstrom, Per
    Olsson, Eleonor
    Veerla, Srinivas
    Gallardo, Alberto
    Sjöblom, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics.
    Chang, Andy C. -M.
    Reddel, Roger R.
    Mangues, Ramon
    Augsten, Martin
    Ostman, Arne
    STC1 Expression By Cancer-Associated Fibroblasts Drives Metastasis of Colorectal Cancer2013In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 74, no 4, p. 1287-1297Article in journal (Refereed)
    Abstract [en]

    Platelet-derived growth factor (PDGF) receptor signaling is a major functional determinant of cancer-associated fibroblasts (CAF). Elevated expression of PDGF receptors on stromal CAFs is associated with metastasis and poor prognosis, but mechanism(s) that underlie these connections are not understood. Here, we report the identification of the secreted glycoprotein stanniocalcin-1 (STC1) as a mediator of metastasis by PDGF receptor function in the setting of colorectal cancer. PDGF-stimulated fibroblasts increased migration and invasion of cocultured colorectal cancer cells in an STC1-dependent manner. Analyses of human colorectal cancers revealed significant associations between stromal PDGF receptor and STC1 expression. In an orthotopic mouse model of colorectal cancer, tumors formed in the presence of STC1-deficient fibroblasts displayed reduced intravasation of tumor cells along with fewer and smaller distant metastases formed. Our results reveal a mechanistic basis for understanding the contribution of PDGF-activated CAFs to cancer metastasis.

  • 21.
    Rasmussen, Markus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sundström, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Kultima, Hanna Göransson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Birgisson, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Isaksson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Allele-specific copy number analysis of tumor samples with aneuploidy and tumor heterogeneity2011In: Genome Biology, ISSN 1465-6906, E-ISSN 1474-760X, Vol. 12, no 10, p. R108-Article in journal (Refereed)
    Abstract [en]

    We describe a bioinformatic tool, Tumor Aberration Prediction Suite (TAPS), for the identification of allele-specific copy numbers in tumor samples using data from Affymetrix SNP arrays. It includes detailed visualization of genomic segment characteristics and iterative pattern recognition for copy number identification, and does not require patient-matched normal samples. TAPS can be used to identify chromosomal aberrations with high sensitivity even when the proportion of tumor cells is as low as 30%. Analysis of cancer samples indicates that TAPS is well suited to investigate samples with aneuploidy and tumor heterogeneity, which is commonly found in many types of solid tumors.

  • 22. Smedh, Kennet
    et al.
    Birgisson, Helgi
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Raab, Yngve
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Strand, Eva
    Karlsson, Catharina
    [Self-expanding stent in obstructing colorectal cancer. A new technique to avoid abdominal surgery]2003In: Lakartidningen, ISSN 0023-7205, Vol. 100, no 22, p. 1982-6Article in journal (Other scientific)
1 - 22 of 22
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