uu.seUppsala University Publications
Change search
Link to record
Permanent link

Direct link
BETA
Bergqvist, Michael
Publications (10 of 51) Show all publications
Lugano, R., Vemuri, K., Yu, D., Bergqvist, M., Smits, A., Essand, M., . . . Dimberg, A. (2018). CD93 promotes integrin-β1 activation and fibronectin fibrillogenesis during tumor angiogenesis.. Journal of Clinical Investigation, Article ID 97459.
Open this publication in new window or tab >>CD93 promotes integrin-β1 activation and fibronectin fibrillogenesis during tumor angiogenesis.
Show others...
2018 (English)In: Journal of Clinical Investigation, ISSN 0021-9738, E-ISSN 1558-8238, article id 97459Article in journal (Refereed) Epub ahead of print
Abstract [en]

Tumor angiogenesis occurs through regulation of genes that orchestrate endothelial sprouting and vessel maturation, including deposition of a vessel-associated extracellular matrix. CD93 is a transmembrane receptor that is up-regulated in tumor vessels in many cancers, including high-grade glioma. Here, we demonstrate that CD93 regulates integrin-β1-signaling and organization of fibronectin fibrillogenesis during tumor vascularization. In endothelial cells and mouse retina, CD93 was found to be expressed in endothelial filopodia and to promote filopodia formation. The CD93 localization to endothelial filopodia was stabilized by interaction with multimerin-2 (MMRN2), which inhibited its proteolytical cleavage. The CD93-MMRN2 complex was required for activation of integrin-β1, phosphorylation of focal adhesion kinase (FAK) and fibronectin fibrillogenesis in endothelial cells. Consequently, tumor vessels in gliomas implanted orthotopically in CD93-deficient mice showed diminished activation of integrin-β1 and lacked organization of fibronectin into fibrillar structures. These findings demonstrate a key role of CD93 in vascular maturation and organization of the extracellular matrix in tumors, identifying it as a potential target for therapy.

Keywords
Brain cancer, Fibronectin, Oncology, Vascular Biology, endothelial cells
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-350902 (URN)10.1172/JCI97459 (DOI)29763414 (PubMedID)
Available from: 2018-05-17 Created: 2018-05-17 Last updated: 2018-09-12Bibliographically approved
Nilsson, J., Holgersson, G., Jaras, J., Bergström, S. & Bergqvist, M. (2018). The role of income in brain tumor patients: a descriptive register-based study. Medical Oncology, 35(4), Article ID 52.
Open this publication in new window or tab >>The role of income in brain tumor patients: a descriptive register-based study
Show others...
2018 (English)In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 35, no 4, article id 52Article in journal (Refereed) Published
Abstract [en]

Socioeconomic status (SES) and its association with cancer in general have been thoroughly studied in the last decades. Several studies have shown associations between SES and many types of cancer such as lung cancer, breast cancer, and prostate cancer. For gliomas, no clear occupational or exposure risk factors have been identified, although some possible risk factors such as use of cellular telephone are still controversial. The aim in the present study is to analyze whether there is an association between SES and development of brain cancer. Data from 1999 through 2013 were collected from the Swedish Cancer Registry and from the National Statistics of Sweden. Age-standardized incidence rates for people with different income were calculated using linear regression model. A total of 11,892 patients were included, of which 5675 were meningiomas, 1216 low-grade gliomas, and 5001 high-grade gliomas. No clear trend between increasing incidence rates and higher income was seen in neither of the investigated brain tumor histologies. In conclusion, the results should be interpreted with caution, but there does not seem to be a correlation in this material between increased income and development of brain cancer.

Place, publisher, year, edition, pages
Springer, 2018
Keywords
Brain cancer, Incidence trend, Income, Cancer Register, Socioeconomic status
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-351691 (URN)10.1007/s12032-018-1108-5 (DOI)000428784500009 ()29532282 (PubMedID)
Available from: 2018-06-04 Created: 2018-06-04 Last updated: 2018-06-04Bibliographically approved
Byström, S., Fredolini, C., Edqvist, P.-H. D., Nyaiesh, E.-N., Drobin, K., Uhlen, M., . . . Schwenk, J. M. (2017). Affinity Proteomics Exploration of Melanoma Identifies Proteins in Serum with Associations to T-Stage and Recurrence. Translational Oncology, 10(3), 385-395
Open this publication in new window or tab >>Affinity Proteomics Exploration of Melanoma Identifies Proteins in Serum with Associations to T-Stage and Recurrence
Show others...
2017 (English)In: Translational Oncology, ISSN 1944-7124, E-ISSN 1936-5233, Vol. 10, no 3, p. 385-395Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Blood-based proteomic profiling may aid and expand our understanding of diseases and their different phenotypes. The aim of the presented study was to profile serum samples from patients with malignant melanoma using affinity proteomic assays to describe proteins in the blood stream that are associated to stage or recurrence of melanoma. MATERIAL AND METHODS: Multiplexed protein analysis was conducted using antibody suspension bead arrays. A total of 232 antibodies against 132 proteins were selected from (i) a screening with 4595 antibodies and 32 serum samples from melanoma patients and controls, (ii) antibodies used for immunohistochemistry, (iii) protein targets previously related with melanoma. The analysis was performed with 149 serum samples from patients with malignant melanoma. Antibody selectivity was then assessed by Western blot, immunocapture mass spectrometry, and epitope mapping. Lastly, indicative antibodies were applied for IHC analysis of melanoma tissues. RESULTS: Serum levels of regucalcin (RGN) and syntaxin 7 (STX7) were found to be lower in patients with both recurring tumors and a high Breslow's thickness (T-stage 3/4) compared to low thickness (T-stage 1/2) without disease recurrence. Serum levels of methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) were instead elevated in sera of T3/4 patients with recurrence. The analysis of tissue sections with S100A6 and MTHFD1L showed positive staining in a majority of patients with melanoma, and S100A6 was significantly associated to T-stage. CONCLUSIONS: Our findings provide a starting point to further study RGN, STX7, MTHFD1L and S100A6 in serum to elucidate their involvement in melanoma progression and to assess a possible contribution to support clinical indications.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-333614 (URN)10.1016/j.tranon.2017.03.002 (DOI)000407707600012 ()28433799 (PubMedID)
Funder
Knut and Alice Wallenberg FoundationScience for Life Laboratory - a national resource center for high-throughput molecular bioscience
Available from: 2017-11-16 Created: 2017-11-16 Last updated: 2017-11-16Bibliographically approved
Nilsson, J., Blomberg, C., Holgersson, G., Carlsson, T., Bergqvist, M. & Bergström, S. (2017). End-of-life care: Where do cancer patients want to die? A systematic review. Asian Perspectives, 13(6), 356-364
Open this publication in new window or tab >>End-of-life care: Where do cancer patients want to die? A systematic review
Show others...
2017 (English)In: Asian Perspectives, ISSN 0066-8435, E-ISSN 1535-8283, ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, ISSN 1743-7555, Vol. 13, no 6, p. 356-364Article, review/survey (Refereed) Published
Abstract [en]

The importance to die at preferred death place is substantial among terminally ill cancer patients. Previously, several studies have investigated this issue, but no systematic review has been made for many years. This systematic review was made in order to investigate preferred death place among cancer patients. A systematic search was made in PubMed library and a total of 399 articles were found, of which 23 were eligible and included in the review. Preference of home death averaged by 59.9% (39.7–100%) across all studies. Information about actual death place was only reported in 12 studies with an average of 40.4% (14–65.2%); thus, the incongruence between preferred and actual death place seems to be substantial. This highlights the importance of health care providers to discuss the issue with the patients and their families. However, study designs must improve and publications of socioeconomic data should be unified to ease interpretation in future studies.

Keywords
palliative end-of-life care, preferred death place
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-356246 (URN)10.1111/ajco.12678 (DOI)000427541000004 ()28294576 (PubMedID)
Available from: 2018-07-27 Created: 2018-07-27 Last updated: 2018-07-27Bibliographically approved
Nilsson, J., Holgersson, G., Carlsson, T., Henriksson, R., Bergström, S. & Bergqvist, M. (2017). Incidence trends in high-grade primary brain tumors in males and females. Oncology Letters, 13(4), 2831-2837
Open this publication in new window or tab >>Incidence trends in high-grade primary brain tumors in males and females
Show others...
2017 (English)In: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 13, no 4, p. 2831-2837Article in journal (Refereed) Published
Abstract [en]

The focus of the present review is to investigate whether there is a variation in the incidence rates between male and female patients with high-grade primary brain tumors and if there are altered incidence rates associated with the time at which they were diagnosed. Previous studies identified in internationally peer-reviewed journals were identified using a systematic search of the PubMed database. Due to the difficulties in data interpretation, studies that exclusively included patient data classified prior to the 2nd edition of the World Health Organization histological classification system of brain tumors were excluded. The overall incidence rates and incidence trends of male and female patients were analyzed separately. The mean age-adjusted overall incidence rate in the male population was 1.27 per 100,000 compared with 0.89 per 100,000 in the female population. The variance between the two genders differed and a Wilcoxon rank-sum test indicated that there was no significant difference in the incidence rate of high-grade primary brain tumors between males and females (P=0.3658). Furthermore, there was no significant difference in incidence rate trend between 1996-2004 and 2005-2010 for male or female populations (P=0.101 and P=0.472, respectively). The results from the present systematic review did not demonstrate a significant difference in incidence rate between the two genders. Therefore, the results from the current study are considered to be preliminary and further studies are required to elucidate this issue.

Keywords
incidence trends, high-grade brain tumors, gender
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-321444 (URN)10.3892/ol.2017.5770 (DOI)000398514200119 ()
Available from: 2017-05-05 Created: 2017-05-05 Last updated: 2017-05-05
Bergqvist, M., Holgersson, G., Bondarenko, I., Grechanaya, E., Maximovich, A., Andor, G., . . . Harmenberg, J. (2017). Phase II randomized study of the IGF-1R pathway modulator AXL1717 compared to docetaxel in patients with previously treated, locally advanced or metastatic non-small cell lung cancer. Acta Oncologica, 53(3), 441-447
Open this publication in new window or tab >>Phase II randomized study of the IGF-1R pathway modulator AXL1717 compared to docetaxel in patients with previously treated, locally advanced or metastatic non-small cell lung cancer
Show others...
2017 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 53, no 3, p. 441-447Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The primary objective of this study was to compare the progression-free survival (PFS) at 12 weeks between patients treated with IGF-1R pathway modulator AXL1717 (AXL) and patients treated with docetaxel (DCT).

MATERIAL AND METHODS: The study was conducted at 19 study centers in five countries. A total of 99 patients with previously treated, locally advanced or metastatic non-small cell lung cancer (NSCLC) of the squamous cell carcinoma (SCC) or adenocarcinoma (AC) subtypes in need of additional treatment were randomized and treated with either 300 or 400 mg of AXL as daily BID treatment (58 patients) or DCT given as 75 mg/m(2) in three-week cycles (41 patients) as monotherapy in a 3:2 ratio for each NSCLC subtype. Patients were treated in the primary study treatment period for a maximum of four treatment cycles.

RESULTS: The 12-week PFS rate, median PFS and overall survival (OS), as well Kaplan-Meier hazard ratio for PFS and OS, did not show any statistically significant differences between the treatment groups. For the primary endpoint, the AXL group had a lower percentage of patients (25.9%) who were progression-free at Week 12 as compared to the DCT group (39.0%), although the difference was not statistically significant. The most notable difference in the incidence of treatment emergent adverse effects (TEAEs) was the lower incidence of treatment-related grade 3/4 neutropenia in patients treated with AXL.

CONCLUSION: These results suggest neither of the treatments to be superior of the other when treating locally advanced or metastatic NSCLC. Considering the lower incidence of grade 3/4 neutropenia in the AXL group this treatment warrants further research.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-312364 (URN)10.1080/0284186X.2016.1253866 (DOI)000396774900011 ()27882820 (PubMedID)
Available from: 2017-01-09 Created: 2017-01-09 Last updated: 2017-11-29Bibliographically approved
Holgersson, G., Bergström, S., Hallqvist, A., Liv, P., Nilsson, J., Willen, L., . . . Bergqvist, M. (2017). The prognostic value of pre-treatment thrombocytosis in two cohorts of patients with non-small cell lung cancer treated with curatively intended chemoradiotherapy. Neoplasma (Bratislava), 64(6), 909-915
Open this publication in new window or tab >>The prognostic value of pre-treatment thrombocytosis in two cohorts of patients with non-small cell lung cancer treated with curatively intended chemoradiotherapy
Show others...
2017 (English)In: Neoplasma (Bratislava), ISSN 0028-2685, E-ISSN 1338-4317, Vol. 64, no 6, p. 909-915Article in journal (Refereed) Published
Abstract [en]

Chemoradiotherapy is the standard of care for inoperable stage III non-small cell lung cancer (NSCLC). This treatment, however, offers only a small chance of cure and is associated with many side effects. Little research has been made concerning which patients benefit most/least from the treatment. The present study evaluates the prognostic value of anemia, leukocytosis and thrombocytosis at diagnosis in this treatment setting. In the present study, data were collected retrospectively for 222 patients from two different phase II studies conducted between 2002-2007 in Sweden with patients treated with chemoradiotherapy for stage IIIA-IIIB NSCLC. Clinical data and the serum values of hemoglobin (Hgb), White blood cells (WBC) and Platelets (Plt) at enrollment were collected for all patients and studied in relation to overall survival using Kaplan-Meier product-limit estimates and a multivariate Cox proportional hazards regression model.

The results showed that patients with thrombocytosis (Plt > 350 x 109/L) had a shorter median overall survival (14.5 months) than patients with normal Plt at baseline (23.7 months). Patients with leukocytosis (WBC > 9 x 109/L) had a shorter median survival (14.9 months) than patients with a normal WBC at baseline (22.5 months). However, in a multivariate model including all lab parameters and clinical factors, only thrombocytosis and performance status displayed a prognostic significance.

In Conclusion, thrombocytosis showed to be an independent prognostic marker associated with shorter overall survival in stage III NSCLC treated with curatively intended chemoradiotherapy. This knowledge can potentially be used together with established prognostic factors, such as performance status when choosing the optimal therapy for the individual patient in this clinical setting.

Keywords
NSCLC, anemia, leukocytosis, thrombocytosis, prognostic, survival
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-339512 (URN)10.4149/neo_2017_614 (DOI)000418756500013 ()28895417 (PubMedID)
Available from: 2018-01-19 Created: 2018-01-19 Last updated: 2018-01-19Bibliographically approved
Nilsson, J., Berglund, A., Bergström, S., Bergqvist, M. & Lambe, M. (2017). The role of comorbidity in the management and prognosis in nonsmall cell lung cancer: a population-based study. Acta Oncologica, 56(7), 949-956
Open this publication in new window or tab >>The role of comorbidity in the management and prognosis in nonsmall cell lung cancer: a population-based study
Show others...
2017 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 56, no 7, p. 949-956Article in journal (Refereed) Published
Abstract [en]

Background: Coexisting disease constitutes a challenge for the provision of optimal cancer care. The influence of comorbidity on lung cancer management and prognosis remains incompletely understood. We assessed the influence of comorbidity on treatment intensity and prognosis in a population-based setting in patients with nonsmall cell lung cancer.Material and methods: Our study was based on information available in Lung Cancer Data Base Sweden (LcBaSe), a database generated by record linkage between the National Lung Cancer Register (NLCR) and several other population-based registers in Sweden. The NLCR includes data on clinical characteristics on 95% of all patients with lung cancer in Sweden since 2002. Comorbidity was assessed using the Charlson Comorbidity Index. Logistic regression and time to event analysis was used to address the association between comorbidity and treatment and prognosis.Results: In adjusted analyses encompassing 19,587 patients with a NSCLC diagnosis and WHO Performance Status 0-2 between 2002 and 2011, those with stage-IA-IIB disease and severe comorbidity were less likely to be offered surgery (OR: 0.45; 95% CI: 0.36-0.57). In late-stage disease (IIIB-IV), severe comorbidity was also associated with lower chemotherapy treatment intensity (OR: 0.76; 95% CI: 0.65-0.89). In patients with early, but not late-stage disease, severe comorbidity in adjusted analyses was associated with an increased all-cause mortality, while lung cancer-specific mortality was largely unaffected by comorbidity burden.Conclusions: Comorbidity contributes to the poor prognosis in NSCLC patients. Routinely published lung cancer survival statistics not considering coexisting disease conveys a too pessimistic picture of prognosis. Optimized management of comorbid conditions pre- and post-NSCLC-specific treatment is likely to improve outcomes.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2017
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-323491 (URN)10.1080/0284186X.2017.1324213 (DOI)000401721200008 ()28486004 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2017-06-22 Created: 2017-06-22 Last updated: 2017-06-22Bibliographically approved
Nilsson, J., Kallman, M., Ostlund, U., Holgersson, G., Bergqvist, M. & Bergström, S. (2016). The Use of Complementary and Alternative Medicine in Scandinavia. Anticancer Research, 36(7), 3243-3251
Open this publication in new window or tab >>The Use of Complementary and Alternative Medicine in Scandinavia
Show others...
2016 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 36, no 7, p. 3243-3251Article, review/survey (Refereed) Published
Abstract [en]

Background: Complementary alternative medicine (CAM) is widely used among patients with cancer. This usage may have potentially harmful effects, especially when combined with anticancer drugs. However, some complementary methods may benefit patients. This review investigated the prevalence of CAM use among patients with cancer in Scandinavia and secondly studied the educational levels of CAM users compared to non-users. Materials and Methods: A systematic search of the PubMed library was carried out to locate articles published between January 2000 and October 2015 that investigated prevalence of CAM use among Scandinavian patients with cancer. Results: Twenty-two articles were found, of which nine were included in the review. The prevalence of CAM use was 7.9% to 53%, with an average of 36.0% across all studies. Conclusion: Use of CAM is widespread among patients with cancer. Knowledge about CAM should be disseminated to both patients and staff in order to optimise discussions about CAM in clinical practice.

Keywords
Complementary alternative medicine, CAM, Scandinavia, review
National Category
Other Health Sciences
Identifiers
urn:nbn:se:uu:diva-300621 (URN)000378867600002 ()27354580 (PubMedID)
Available from: 2016-08-10 Created: 2016-08-10 Last updated: 2018-02-26Bibliographically approved
Holgersson, G., Bergström, S., Liv, P., Nilsson, J., Edlund, P., Blomberg, C., . . . Bergqvist, M. (2015). Effect of Increased Radiotoxicity on Survival of Patients with Non-small Cell Lung Cancer Treated with Curatively Intended Radiotherapy. Anticancer Research, 35(10), 5491-5497
Open this publication in new window or tab >>Effect of Increased Radiotoxicity on Survival of Patients with Non-small Cell Lung Cancer Treated with Curatively Intended Radiotherapy
Show others...
2015 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 35, no 10, p. 5491-5497Article in journal (Refereed) Published
Abstract [en]

Aim: To elucidate the impact of different forms of radiation toxicities (esophagitis, radiation pneumonitis, mucositis and hoarseness), on the survival of patients treated with curatively intended radiotherapy for non-small cell lung cancer (NSCLC). Patients and Methods: Data were individually collected retrospectively for all patients diagnosed with NSCLC subjected to curatively intended radiotherapy (>= 50 Gy) in Sweden during the time period 1990 to 2000. Results: Esophagitis was the only radiation-induced toxicity with an impact on survival (hazard ratio=0.83, p=0.016). However, in a multivariate model, with clinical-and treatment-related factors taken into consideration, the impact of esophagitis on survival was no longer statistically significant (hazard ratio=0.88, p=0.17). Conclusion: The effect on survival seen in univariate analysis may be related to higher radiation dose and to the higher prevalence of chemotherapy in this group. The results do not suggest that the toxicities examined have any detrimental effect on overall survival.

Keywords
NSCLC, radiotherapy, toxicity, esophagitis, survival
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-265679 (URN)000361823200042 ()26408714 (PubMedID)
Available from: 2015-11-04 Created: 2015-11-02 Last updated: 2017-12-01Bibliographically approved
Organisations

Search in DiVA

Show all publications