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  • 151. Zheng, Jiaojiao
    et al.
    Rutegård, Martin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Santoni, Giola
    Wallner, Bengt
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Xie, Shao-Hua
    Lagergren, Jesper
    Prediabetes and diabetes in relation to risk of gastric adenocarcinoma2019In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 120, no 12, p. 1147-1152Article in journal (Refereed)
    Abstract [en]

    Background: Whether prediabetes or diabetes increases the risk of gastric adenocarcinoma is not clear.

    Methods: This cohort study included 111,198 participants in the Northern Swedish Health and Disease Study. The participants were followed up from November 1985 to April 2017. The exposure to prediabetes or diabetes was assessed by oral glucose tolerance tests and self-reports. The incidence of the outcome gastric adenocarcinoma was identified from the Swedish Cancer Registry. Multivariable Cox regressions were used to analyse the associations between prediabetes or diabetes and the risk of gastric adenocarcinoma, providing hazard ratios (HR) with 95% confidence intervals (CI), with adjustment for sex, age, calendar year, body mass index, tobacco smoking and education level.

    Results: Compared with normoglycaemic participants, the risk of gastric adenocarcinoma was not increased among participants with prediabetes (HR 1.07, 95% CI 0.79–1.44), diabetes (HR 0.77, 95% CI 0.46–1.29) or any of these exposures (HR 0.96, 95% CI 0.73–1.27). No associations were identified between prediabetes or diabetes and the risk of gastric adenocarcinoma in stratified analyses or in analyses separating cardia and non-cardia gastric adenocarcinoma.

    Conclusions: This study does not support the hypothesis that prediabetes or diabetes increases the risk of gastric adenocarcinoma.

  • 152.
    Öhlund, Daniel
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Ardnor, Bjarne
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Öman, Mikael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Naredi, Peter
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Expression pattern and circulating levels of endostatin in patients with pancreas cancer2008In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 122, no 12, p. 2805-2810Article in journal (Refereed)
    Abstract [en]

    Endostatin is a potent inhibitor of angiogenesis that is cleaved from the basement membrane protein type XVIII collagen. Expression of endostatin has recently been shown by Western blot analysis of tissue lysates in normal pancreas and pancreas cancer tissue. We show here that the expression pattern of type XVIII collagen/endostatin is shifted from a general basement membrane staining and is mainly located in the vasculature during tumor progression. This shift in type XVIII collagen/endostatin expression pattern coincides with an up-regulation of MMPs involved in endostatin processing in the tumor microenvironment, such as MMP-3, MMP-9 and MMP-13. The circulating levels of endostatin was analyzed in patients with pancreas cancer and compared to that of healthy controls, as well as after surgical treatment or in a group of nonoperable patients after intraperitoneal fluorouracil (5-FU) chemotherapy. The results show that patients with pancreas cancer have increased circulating levels of endostatin and that these levels are normalized after surgery or intraperitoneal chemotherapy. These findings indicate that endostatin could be used as a biomarker for pancreas cancer progression.

  • 153.
    Öhlund, Daniel
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Franklin, Oskar
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lundberg, Erik
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lundin, Christina
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Type IV collagen enhances pancreatic cancer cell proliferation and migration through an autocrine loopManuscript (preprint) (Other academic)
  • 154.
    Öhlund, Daniel
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Franklin, Oskar
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lundberg, Erik
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lundin, Christina
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Type IV collagen stimulates pancreatic cancer cell proliferation, migration, and inhibits apoptosis through an autocrine loop2013In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 13, article id 154Article in journal (Refereed)
    Abstract [en]

    Background: Pancreatic cancer shows a highly aggressive and infiltrative growth pattern and is characterized by an abundant tumor stroma known to interact with the cancer cells, and to influence tumor growth and drug resistance. Cancer cells actively take part in the production of extracellular matrix proteins, which then become deposited into the tumor stroma. Type IV collagen, an important component of the basement membrane, is highly expressed by pancreatic cancer cells both in vivo and in vitro. In this study, the cellular effects of type IV collagen produced by the cancer cells were characterized.

    Methods: The expression of type IV collagen and its integrin receptors were examined in vivo in human pancreatic cancer tissue. The cellular effects of type IV collagen were studied in pancreatic cancer cell lines by reducing type IV collagen expression through RNA interference and by functional receptor blocking of integrins and their binding-sites on the type IV collagen molecule.

    Results: We show that type IV collagen is expressed close to the cancer cells in vivo, forming basement membrane like structures on the cancer cell surface that colocalize with the integrin receptors. Furthermore, the interaction between type IV collagen produced by the cancer cell, and integrins on the surface of the cancer cells, are important for continuous cancer cell growth, maintenance of a migratory phenotype, and for avoiding apoptosis.

    Conclusion: We show that type IV collagen provides essential cell survival signals to the pancreatic cancer cells through an autocrine loop.

  • 155.
    Öhlund, Daniel
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lundin, Christina
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Ardnor, Bjarne
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Öman, Mikael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Naredi, Peter
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Type IV collagen is a tumour stroma-derived biomarker for pancreas cancer2009In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 101, no 1, p. 91-97Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Pancreas cancer is a dreaded disease with high mortality, despite progress in surgical and oncological treatments in recent years. The field is hampered by a lack of good prognostic and predictive tumour biomarkers to be used during follow-up of patients.

    METHODS: The circulating level of type IV collagen was measured by ELISA in pancreas cancer patients and controls. The expression pattern of type IV collagen in normal pancreas, pancreas cancer tissue and in pancreas cancer cell lines was studied by immunofluorescence and Western blot techniques.

    RESULTS: Patients with pancreas cancer have significantly increased circulating levels of type IV collagen. In pancreas cancer tissue high levels of type IV collagen expression was found in close proximity to cancer cells in the tumour stroma. Furthermore, pancreas cancer cells were found to produce and secrete type IV collagen in vitro, which in part can explain the high type IV collagen expression observed in pancreas cancer tissue, and the increased circulating levels in pancreas cancer patients. Of clinical importance, our results show that the circulating level of type IV collagen after surgery is strongly related to prognosis in patients treated for pancreas cancer by pancreatico-duodenectomy with curative intent. Persisting high levels of circulating type IV collagen after surgery indicates a quick relapse in disease and poor survival.

    CONCLUSION: Our results most importantly show that stroma related substances can be evaluated as potential cancer biomarkers, and thereby underline the importance of the tumour microenvironment also in this context.

  • 156.
    Öhlund, Daniel
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lundin, Christina
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Öman, Mikael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Naredi, Peter
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Basement membrane fragments as pancreatic tumour markers: a comparison to conventional markersManuscript (preprint) (Other academic)
  • 157.
    GlobalSurg Collaborative, (Contributor)
    NIHR Unit on Global Surgery (Universities of Birmingham, Edinburgh and Warwick), University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, UK.
    Sund, Malin (Contributor)
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Andersson, Linda (Contributor)
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Gunnarsson, Ulf (Contributor)
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study2018In: Surgical Endoscopy, ISSN 0930-2794, E-ISSN 1432-2218, Vol. 32, no 8, p. 3450-3466Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide.

    METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days.

    RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45).

    CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments.

    TRIAL REGISTRATION: NCT02179112.

  • 158.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study.2018In: Lancet. Infectious diseases (Print), ISSN 1473-3099, E-ISSN 1474-4457, Vol. 18, no 5, p. 516-525, article id S1473-3099(18)30101-4Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world.

    METHODS: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231.

    FINDINGS: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p<0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05-2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p<0·001).

    INTERPRETATION: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication.

    FUNDING: DFID-MRC-Wellcome Trust Joint Global Health Trial Development Grant, National Institute of Health Research Global Health Research Unit Grant.

1234 151 - 158 of 158
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