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Spångeus, Anna
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Publications (10 of 17) Show all publications
Jonsson, E., Hansson-Hedblom, A., Ljunggren, Ö., Åkesson, K., Spångeus, A., Kanis, J. A. & Borgström, F. (2018). A health economic simulation model for the clinical management of osteoporosis. Osteoporosis International, 29(3), 545-555
Open this publication in new window or tab >>A health economic simulation model for the clinical management of osteoporosis
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2018 (English)In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 29, no 3, p. 545-555Article in journal (Refereed) Published
Abstract [en]

The objective was to estimate the burden of osteoporosis in Sweden based on current clinical practice and the cost-effectiveness of improvements in the management of osteoporosis over the clinical management compared to current clinical practice. Results showed that better compliance to treatment guidelines is associated with better projected outcomes and cost-savings.

INTRODUCTION: The purpose of this study is to estimate the burden of osteoporosis in Sweden based on current clinical practice and the cost-effectiveness of improvements in the management of osteoporosis over the clinical management compared to current clinical practice.

METHODS: The analysis was carried out using a model that simulates the individual patients considered for pharmacological treatment during 1 year and their projected osteoporosis treatment pathway, quality-adjusted life years (QALYs) and costs over their remaining lifetime. All patients regardless of treatment or no treatment were simulated. Information on current management of osteoporosis in terms of patient characteristics and treatment patterns were derived from a Swedish osteoporosis research database based on national registers and patient records. Current (standard) clinical management was compared with alternative scenarios mirroring Swedish treatment guidelines.

RESULTS: The national burden in terms of lost QALYs was estimated at 14,993 QALYs and the total economic cost at €776M. Scenario analyses showed that 382-3864 QALYs could be gained at a cost/QALY ranging from cost-saving to €31368, depending on the scenario. The margin of investment, i.e. the maximum amount that could be invested in the healthcare system to achieve these improvements up to the limit of the willingness to pay/QALY, was estimated at €199M on a population level (€3,634/patient).

CONCLUSIONS: The analysis showed that better compliance to treatment guidelines is associated with better projected outcomes and cost-savings. From a cost-effectiveness perspective, there is also considerable room for investment to achieve these improvements in the management of osteoporosis.

Place, publisher, year, edition, pages
Springer London, 2018
Keywords
Cost, Fracture, Osteoporosis, Quality-of-life, Register, Sweden
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:liu:diva-144030 (URN)10.1007/s00198-017-4325-4 (DOI)000426646900003 ()29196775 (PubMedID)2-s2.0-85035789527 (Scopus ID)
Note

Funding agencies:  Medtronic

Available from: 2018-01-04 Created: 2018-01-04 Last updated: 2018-04-11Bibliographically approved
Woisetschläger, M. & Spångeus, A. (2018). Model for improved correlation of BMD values between abdominal routine Dual energy CT data and DXA scans. European Journal of Radiology, 99, 76-81
Open this publication in new window or tab >>Model for improved correlation of BMD values between abdominal routine Dual energy CT data and DXA scans
2018 (English)In: European Journal of Radiology, ISSN 0720-048X, E-ISSN 1872-7727, Vol. 99, p. 76-81Article in journal (Refereed) Published
Abstract [en]

Background

Osteoporosis is a common but underdiagnosed and undertreated disease causing severe morbidity and economic burden. The gold standard for detection of osteoporosis is DXA (dual energy x-ray absorptiometry), which is a dedicated examination for osteoporosis. Dual energy CT (DECT) examinations are increasingly used in daily routine for a wide variety of diagnoses. In the present study, we wanted to examine whether vBMD (volume bone mass density) could be evaluated as a side product in non-contrast as well as contrast phases as well as to evaluate a correction model taking known shortcomings for DXA into account.

Methods

A total of 20 patients, i.e. 79 vertebrae (one excluded due to vertebral fracture), mean age 71 years (range 43–85) with a mean BMI (body mass index) of 26 (range 17–33) were examined with both abdominal/pelvic DECT as well as DXA. Furthermore, aortic calcium was measured as well as the presence of osteoarthritis of the spine (OAS) and osteoarthritis in facet joints (OAF) with a 5-grade scaling system.

Results

A significant correlation was found between DXA BMD and vBMD from DECT with no contrast (WNC) (r = 0.424, p = 0.001), and with venous contrast (WVC) (r = 0.402, p < 0.001), but no significant correlation was found with arterial contrast (WAC). Using multivariate linear regression with DXA BMD as dependent, two models were created combining DECT WNC, aortic calciumscore (ACS), OAS and BMI yielding an R2 = 0.616 (model 1) and replacement of WNC to WVC a R2 = 0.612 (model 2). The Pearson correlation between DXA and predictive DXA BMD value of model 1 was r = 0.785 (p < 0.001) and model 2 r = 0.782 (p < 0.001).

Conclusion

There is a correlation between DXA BMD and DECT in non-contrast and venous contrast scans but not in arterial scans. The correlation is further improved by quantifying the degree of different confounding factors (osteoarthritis of the spine, body mass index and aortic calcium score) and taking these into account in an explanatory model. Future software solutions with DECT data as input data might be able to automatically measure the BMD in the trabecular bone as well as measuring the confounding factors automatically in order to obtain spinal DXA comparable BMD values.

Keywords
Osteoporosis;Bone mass density;Dual-energy CT;DXA;Osteoarthritis of the spine;Aortic calcium score
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-144039 (URN)10.1016/j.ejrad.2017.12.017 (DOI)000423344100010 ()29362154 (PubMedID)
Funder
Östergötland County Council
Note

Funding agencies: Medical Research Council of south east Sweden; ALF grants, Region Ostergotland, Sweden

Available from: 2018-01-05 Created: 2018-01-05 Last updated: 2018-02-12
Woisetschläger, M. & Spångeus, A. (2018). Model for improved correlation of BMD values between abdominal routine dual-energy CT data and DXA scans. In: : . Paper presented at European Congress of Radiology, Vienna, February 28 - March 4, Vienna, Italy.
Open this publication in new window or tab >>Model for improved correlation of BMD values between abdominal routine dual-energy CT data and DXA scans
2018 (English)Conference paper, Oral presentation with published abstract (Other academic)
Abstract [en]

Background:

Osteoporosis is a common but underdiagnosed and undertreated disease causing severe morbidity and economic burden. The gold standard for detection of osteoporosis is DXA (dual energy x-ray absorptiometry), which is a dedicated examination for osteoporosis. Dual energy CT (DECT) examinations are increasingly used in daily routine for a wide variety of diagnoses. In the present study, we wanted to examine whether vBMD (volume bone mass density) could be evaluated as a side product in non-contrast as well as contrast phases as well as to evaluate a correction model taking known shortcomings for DXA into account. 

Methods:

A total of 20 patients, i.e. 79 vertebrae (one excluded due to vertebral fracture), mean age 71 years (range 43 – 85) with a mean BMI (body mass index) of 26 (range 17 – 33) were examined with both abdominal/pelvic DECT as well as DXA.  Furthermore, aortic calcium was measured as well as the presence of osteoarthritis of the spine (OAS) and osteoarthritis in facet joints (OAF) with a 5-grade scaling system. 

Results:

A significant correlation was found between DXA BMD and vBMD from DECT without with no contrast (WNC) (r=0.424, p=0.001), and with venous contrast (WVC) (r=0.402, p<0.001), but no significant correlation was found with arterial contrast (WAC). Using multivariate linear regression with DXA BMD as dependent, two models were created combining DECT WNC, aortic calciumscore (ACS), OAS and BMI yielding an R2 = 0.616 (model 1) and replacement of WNC to WVC a R2 = 0.612 (model 2).  The Pearson correlation between DXA and predictive DXA BMD value of model 1 was r = 0.785 (p<0.001) and model 2 r = 0.782 (p<0.001).

Conclusion:

There is a correlation between DXA BMD and DECT in non-contrast and venous contrast scans but not in arterial scans. The correlation is further improved by quantifying the degree of different confounding factors (osteoarthritis of the spine, body mass index and aortic calcium score) and taking these into account in an explanatory model. Future software solutions with DECT data as input data might be able to automatically measure the BMD in the trabecular bone as well as measuring the confounding factors automatically in order to obtain spinal DXA comparable BMD values.

Keywords
osteoporosis, bone mass density, computed tomography, dual energy
National Category
Orthopaedics
Identifiers
urn:nbn:se:liu:diva-145654 (URN)
Conference
European Congress of Radiology, Vienna, February 28 - March 4, Vienna, Italy
Projects
Osteoporosprojekt PreFROST
Funder
Östergötland County Council
Available from: 2018-03-13 Created: 2018-03-13 Last updated: 2018-03-23Bibliographically approved
Tjomsland, V., Bojmar, L., Sandström, P., Bratthall, C., Messmer, D., Spångeus, A. & Larsson, M. (2013). IL-1α Expression in Pancreatic Ductal Adenocarcinoma Affects the Tumor Cell Migration and Is Regulated by the p38MAPK Signaling Pathway. PLoS ONE, 8(8)
Open this publication in new window or tab >>IL-1α Expression in Pancreatic Ductal Adenocarcinoma Affects the Tumor Cell Migration and Is Regulated by the p38MAPK Signaling Pathway
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2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 8Article in journal (Refereed) Published
Abstract [en]

The interplay between the tumor cells and the surrounding stroma creates inflammation, which promotes tumor growth and spread. The inflammation is a hallmark for pancreatic adenocarcinoma (PDAC) and is to high extent driven by IL-1α. IL-1α is expressed and secreted by the tumor cells and exerting its effect on the stroma, i.e. cancer associated fibroblasts (CAF), which in turn produce massive amount of inflammatory and immune regulatory factors. IL-1 induces activation of transcription factors such as nuclear factor-κβ (NF-κβ), but also activator protein 1 (AP-1) via the small G-protein Ras. Dysregulation of Ras pathways are common in cancer as this oncogene is the most frequently mutated in many cancers. In contrast, the signaling events leading up to the expression of IL-1α by tumor cells are not well elucidated. Our aim was to examine the signaling cascade involved in the induction of IL-1α expression in PDAC. We found p38MAPK, activated by the K-Ras signaling pathway, to be involved in the expression of IL-1α by PDAC as blocking this pathway decreased both the gene and protein expression of IL-1α. Blockage of the P38MAPK signaling in PDAC also dampened the ability of the tumor cell to induce inflammation in CAFs. In addition, the IL-1α autocrine signaling regulated the migratory capacity of PDAC cells. Taken together, the blockage of signaling pathways leading to IL-1α expression and/or neutralization of IL-1α in the PDAC microenvironment should be taken into consideration as possible treatment or complement to existing treatment of this cancer.

Place, publisher, year, edition, pages
Public Library of Science, 2013
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-97445 (URN)10.1371/journal.pone.0070874 (DOI)000323097300061 ()
Note

Funding Agencies|Swedish Research Council|AI52731|VINNMER (Vinnova)||Medical Research Council of Southeast Sweden||Swedish Society of Medicine||

Available from: 2013-09-12 Created: 2013-09-12 Last updated: 2017-12-06
Spångeus, A., Wijkman, M., Lindström, T., Engvall, J., Östgren, C. J., Nyström, F. H. & Länne, T. (2013). Toe brachial index in middle aged patients with diabetes mellitus type 2: Not just a peripheral issue. Diabetes Research and Clinical Practice, 100(2), 195-202
Open this publication in new window or tab >>Toe brachial index in middle aged patients with diabetes mellitus type 2: Not just a peripheral issue
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2013 (English)In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 100, no 2, p. 195-202Article in journal (Refereed) Published
Abstract [en]

Aim

To explore risk factors for peripheral arterial disease (PAD) as well as the association between toe blood pressure and subclinical and clinical central vascular disease in patients with type 2 diabetes.

Method

Toe brachial index (TBI) was cross-sectionally analyzed in 742 middle-aged (54–66 years) patients with type 2 diabetes as well as non-diabetic controls and related to other vascular measures (e.g. carotid intima media thickness (IMT), presence of carotid plaque, central arterial stiffness and left ventricular mass index) and previous cardiovascular events.

Results

A TBI ≤ 0.7 was seen in 22% of the patients but only one patient had severe TBI reduction (TBI ≤ 0.3). The corresponding figures in the controls were 13% and 0%, respectively. Mean TBI was significantly lower in patients with type 2 diabetes than in controls (0.81 ± 0.14 vs. 0.87 ± 0.15, p < 0.001). In patients with diabetes, a lower TBI was associated with increased central arterial stiffness (p < 0.001), IMT (p < 0.001) and carotid plaque (p < 0.001) as well as with decreasing glomerular filtration rate (p < 0.001). Lower TBI was found in patients with previous macrovascular ischemic events. Furthermore, TBI was negatively correlated with age (p < 0.001), diabetes duration (p < 0.001) and HbA1c (p = 0.01).

Conclusion

PAD, assessed with TBI, is common in a Swedish middle-aged diabetes type 2 cohort, affecting about one-fifth. As ankle pressure may be confounded by falsely high values in patients with diabetes due to media calcification we conclude that information about TBI may improve the risk evaluation regarding arteriosclerotic disease in both small and large vessels in type 2 diabetes.

Place, publisher, year, edition, pages
Elsevier, 2013
Keywords
Diabetes mellitus, Toe pressure, Toe brachial index, Cardiovascular
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-95976 (URN)10.1016/j.diabres.2013.03.004 (DOI)000320590900015 ()
Note

Funding Agencies|Medical Research Council of Southeast Sweden||King Gustav V and Queen Victorias foundation||Center for Medical Image Science and Visualization (CMIV)||Linkoping University||County Council of Ostergotland||GE Healthcare||Swedish Heart-Lung Foundation||Swedish Research Council|12661|Diabetes Research Center||

Available from: 2013-08-19 Created: 2013-08-12 Last updated: 2017-12-06
Rejler, M., Tholstrup, J., Elg, M., Spångéus, A. & Andersson Gäre, B. (2012). Framework for assessing quality of care for inflammatory bowel disease in Sweden. World Journal of Gastroenterology, 18(10), 1085-1092
Open this publication in new window or tab >>Framework for assessing quality of care for inflammatory bowel disease in Sweden
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2012 (English)In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 18, no 10, p. 1085-1092Article in journal (Refereed) Published
Abstract [en]

AIM: To create and apply a framework for quality assessment and improvement in care for inflammatory bowel disease (IBD) patients. less thanbrgreater than less thanbrgreater thanMETHODS A framework for quality assessment and improvement was created for IBD based on two generally acknowledged quality models. The model of Donabedian (Df) offers a logistical and productive perspective and the Clinical Value Compass (CVC) model adds a management and service perspective. The framework creates a pedagogical tool to understand the balance between the dimensions of clinical care (CVC) and the components of clinical outcome (Df). The merged models create a framework of the care process dimensions as a whole, reflecting important parts of the IBD care delivery system in a local setting. Clinical and organizational quality measures were adopted from clinical experience and the literature and were integrated into the framework. Data were collected at the yearly check-up for 481 IBD patients during 2008. The application of the quality assessment framework was tested and evaluated in a local clinical IBD care setting in Jonkoping County, Sweden. less thanbrgreater than less thanbrgreater thanRESULTS: The main outcome was the presentation of how locally-selected clinical quality measures, integrated into two complementary models to develop a framework, could be instrumental in assessing the quality of care delivered to patients with IBD. The selected quality measures of the framework noted less anemia in the population than previously reported, provided information about hospitalization rates and the few surgical procedures reported, and noted good access to the clinic. less thanbrgreater than less thanbrgreater thanCONCLUSION: The applied local quality framework was feasible and useful for assessing the quality of care delivered to IBD patients in a local setting.

Place, publisher, year, edition, pages
Baishideng Publishing Group Co. Limited, 2012
Keywords
Quality measures, Inflammatory bowel disease, Value compass, Donabedian, Quality improvement
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-76615 (URN)10.3748/wjg.v18.i10.1085 (DOI)000301627900011 ()
Note

Funding Agencies|Futurum Research Council||Jonkoping County Council||Foundation for Clinical Cancer Research in Jonkoping County||VINNVARD-research program||

Available from: 2012-04-13 Created: 2012-04-13 Last updated: 2017-12-07
Rejler, M., Tholstrup, J., Andersson-Gare, B. & Spångeus, A. (2012). Low prevalence of anemia in inflammatory bowel disease: A population-based study in Sweden. Scandinavian Journal of Gastroenterology, 47(8-9), 937-942
Open this publication in new window or tab >>Low prevalence of anemia in inflammatory bowel disease: A population-based study in Sweden
2012 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 47, no 8-9, p. 937-942Article in journal (Refereed) Published
Abstract [en]

Objective. Anemia is a well-known complication of inflammatory bowel disease (IBD) with a reported prevalence of 8.8-73.7%. However, knowledge is sparse about the anemia prevalence in a population-based cohort of patients affected by IBD. Materials and methods. The aim of this retrospective, descriptive, population-based study was to determine and analyze the prevalence of anemia for ambulatory (n = 485) as well as for hospitalized patients diagnosed with IBD in 2008 in the Highland Health Care District, Jonkopings County, Sweden. Results. The prevalence of anemia at the annual follow-up in the studied IBD population was 6%, 5% for patients with ulcerative colitis (UC), and 9% for those with Crohns disease (CD). There was a higher rate of anemia at the yearly check up in patients requiring inpatient care during the year. IBD patients, prescribed anti-TNF-alpha treatment, had a higher rate of anemia. Of the hospitalized UC and CD patients (n = 31), 35% and 50%, respectively, had anemia at admission and 6% and 4% had severe anemia (Hb andlt;100 g/L), respectively. Conclusions. The prevalence of anemia in this population was lower than reported previously, probably due to inclusion of all IBD patients in the area in combination with a proactive follow-up model. The prevalence of anemia in this IBD population was similar to the prevalence in the general population. This may indicate that efforts by health care professionals to prevent, identify, and treat anemia in the IBD population have been successful.

Place, publisher, year, edition, pages
Informa Healthcare, 2012
Keywords
anemia, annual follow-up, hospitalization, inflammatory bowel disease, population-based study quality, prevalence
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-82062 (URN)10.3109/00365521.2012.672590 (DOI)000308213200009 ()
Note

Funding Agencies|Futurum Research Council||Jonkoping County Council||Foundation for Clinical Cancer Research in Jonkoping County||VINNVARD||

Available from: 2012-10-01 Created: 2012-09-28 Last updated: 2017-12-07
Tjomsland, V., Spångeus, A., Välilä, J., Sandström, P., Borch, K., Druid, H., . . . Larsson, M. (2011). Interleukin 1α sustains the expression of inflammatory factors in human pancreatic cancer microenvironment by targeting cancer-associated fibroblasts. Neoplasia, 13(8), 664-675
Open this publication in new window or tab >>Interleukin 1α sustains the expression of inflammatory factors in human pancreatic cancer microenvironment by targeting cancer-associated fibroblasts
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2011 (English)In: Neoplasia, ISSN 1522-8002, E-ISSN 1476-5586, Vol. 13, no 8, p. 664-675Article in journal (Refereed) Published
Abstract [en]

The tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC) is dynamic with an extensive interaction between the stroma and tumor cells. The aim for this study was to delineate the cross-talk between PDAC and cancer-associated fibroblasts (CAFs) with focus on the mechanism creating the chronic inflammatory tumor milieu. We assessed the effects of the cross-talk between primary PDAC and CAF cell lines on the creation and sustenance of the inflammatory tumor microenvironment in pancreatic cancer. The coculture of primary PDAC and CAF cell lines enhanced the levels of inflammatory factors including IL-1á, IL-6, CXCL8, VEGFA, CCL20, and COX-2. CAFs were superior to tumor cells regarding the production of most inflammatory factors and tumor cell associated IL-1á was established as the initiator of the enhanced production of inflammatory factors through the binding of IL-1á to the active IL-1 receptor (IL-1R1) expressed predominantly by CAFs. Furthermore, we found a positive correlation between IL-1á and CXCL8 expression levels in PDAC tissues and correlation between IL-1á expression and the clinical outcome of the patients. This confirmed an important role for the IL-1 signaling cascade in the creation and sustenance of a tumor favorable microenvironment. Neutralization of the IL-1á signaling efficiently diminished the cross-talk induced production of inflammatory factors. These data suggest that the cross-talk between PDAC cells and the main stroma cell type, i.e. CAFs, is one essential factor in the formation of the inflammatory tumor environment and we propose that neutralization of the IL-1á signaling might be a potential therapy for this cancer.

Place, publisher, year, edition, pages
Neoplasia Press, 2011
Keywords
Pancreatic cancer, IL-1alpha, cancer associated fibroblasts, cross-talk
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-69954 (URN)10.1593/neo.11332 (DOI)000295942500001 ()21847358 (PubMedID)
Available from: 2011-08-09 Created: 2011-08-09 Last updated: 2017-12-08
Tjomsland, V., Niklasson, L., Sandström, P., Borch, K., Druid, H., Bratthall, C., . . . Spångeus, A. (2011). The Desmoplastic Stroma Plays an Essential Role in the Accumulation and Modulation of Infiltrated Immune Cells in Pancreatic Adenocarcinoma. Clinical & Developmental Immunology, 2011(212810)
Open this publication in new window or tab >>The Desmoplastic Stroma Plays an Essential Role in the Accumulation and Modulation of Infiltrated Immune Cells in Pancreatic Adenocarcinoma
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2011 (English)In: Clinical & Developmental Immunology, ISSN 1740-2522, E-ISSN 1740-2530, Vol. 2011, no 212810Article in journal (Refereed) Published
Abstract [en]

Tumor microenvironment is composed of tumor cells, fibroblasts, and infiltrating immune cells, which all work together and create an inflammatory environment favoring tumor progression. The present study aimed to investigate the role of the desmoplastic stroma in pancreatic ductal adenocarcinoma (PDAC) regarding expression of inflammatory factors and infiltration of immune cells and their impact on the clinical outcome. The PDAC tissues examined expressed significantly increased levels of immunomodulatory and chemotactic factors (IL-6, TGF beta, IDO, COX-2, CCL2, and CCL20) and immune cell-specific markers corresponding to macrophages, myeloid, and plasmacytoid dendritic cells (DCs) as compared to controls. Furthermore, short-time survivors had the lowest levels of DC markers. Immunostainings indicated that the different immune cells and inflammatory factors are mainly localized to the desmoplastic stroma. Therapies modulating the inflammatory tumor microenvironment to promote the attraction of DCs and differentiation of monocytes into functional DCs might improve the survival of PDAC patients.

Place, publisher, year, edition, pages
Hindawi Publishing Corporation, 2011
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-76217 (URN)10.1155/2011/212810 (DOI)000298696600001 ()
Note
Funding Agencies|Swedish Research Council|AI52731|Swedish International Development Cooperation Agency (SIDA)||VINN-MER (Vinnova)||Medical Research Council of Southeast Sweden||Swedish Society of Medicine||Foundation for Clinical Cancer Research in Jonkoping, Sweden||Available from: 2012-03-30 Created: 2012-03-30 Last updated: 2017-12-07
Tjomsland, V., Spångeus, A., Välilä, J., Sandström, P., Borch, K., Druid, H., . . . Larsson, M. (2010). IL-1α Sustains the Inflammation in Human Pancreatic Cancer Microenvironment by Targeting Cancer Associated Fibroblasts. , 10(87)
Open this publication in new window or tab >>IL-1α Sustains the Inflammation in Human Pancreatic Cancer Microenvironment by Targeting Cancer Associated Fibroblasts
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2010 (English)Manuscript (preprint) (Other academic)
Abstract [en]

The tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC) is dynamic with an extensive interaction between the stroma and tumor cells. Our aim for this study was to delineate the cross-talk between PDAC and cancer-associated fibroblasts (CAFs) with focus on the mechanism creating the chronic inflammatory tumor milieu. We assessed the effect cross talk between primary PDAC and CAF cell lines propagated from tumors had on the creation and sustenance of an inflammatory environment and what factors that were involved in establishing the inflammation.

The coculture of PDAC and CAF cell lines, propagated from tumor tissues, enhanced the levels of inflammatory factors including IL-1α, IL-6, CXCL8, VEGFA, CCL20, and COX-2. The production of these factors correlated with the expression detected in vivo in PDAC tissues. The key producers of nearly all inflammatory factors were the CAFs and not the tumor cells.

IL-1α was produced by the tumor cell lines, whereas almost all IL-1RI was expressed by CAFs thus corresponding to their in vivo expression profile in PDAC tissues, indicating a role for the IL-1 signaling cascade in a tumor favorable microenvironment. Neutralization of the IL-1α pathway efficiently diminished the cross talk induced production of inflammatory factors, both in stroma and tumor cells. These data suggest that the cross-talk between PDAC cells and the main stroma cell type, i.e. CAFs, is one contributing factor in the formation of the inflammatory tumor environment and we propose that the neutralization of IL-1α pathway might be a potential therapy for this cancer.

Keywords
Tumor stroma cross talk; pancreatic cancer; cancer associated fibroblasts; inflammation; IL-1α
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-67750 (URN)
Available from: 2011-04-26 Created: 2011-04-26 Last updated: 2011-04-26Bibliographically approved
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