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Bergqvist, Michael
Publications (10 of 48) Show all publications
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
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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., 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
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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.

Keyword
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
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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
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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.

Keyword
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
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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
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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.

Keyword
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
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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.

Keyword
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
Sooman, L., Freyhult, E., Jaiswal, A., Navani, S., Edqvist, P.-H., Pontén, F., . . . Ekman, S. (2015). FGF2 as a potential prognostic biomarker for proneural glioma patients. Acta Oncologica, 54(3), 385-394
Open this publication in new window or tab >>FGF2 as a potential prognostic biomarker for proneural glioma patients
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2015 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 54, no 3, p. 385-394Article in journal (Refereed) Published
Abstract [en]

Background. The survival of high-grade glioma patients is poor and the treatment of these patients can cause severe side effects. This fosters the necessity to identify prognostic biomarkers, in order to optimize treatment and diminish unnecessary suffering of patients. The aim of this study was to identify prognostic biomarkers for high-grade glioma patients.

Methods. Eleven proteins were selected for analysis due to their suggested importance for survival of patients with other types of cancers and due to a high variation in protein levels between glioma patients (according to the Human Protein Atlas, www.proteinatlas.org). Protein expression patterns of these 11 proteins were analyzed by immunohistochemistry in tumor samples from 97 high-grade glioma patients. The prognostic values of the proteins were analyzed with univariate and multivariate Cox regression analyses for the high-grade glioma patients, including subgroup analyses of histological subtypes and immunohistochemically defined molecular subtypes.

Results. The proteins with the most significant (univariate and multivariate p < 0.05) correlations were analyzed further with cross-validated Kaplan-Meier analyses for the possibility of predicting survival based on the protein expression pattern of the corresponding candidate. Random Forest classification with variable subset selection was used to analyze if a protein signature consisting of any combination of the 11 proteins could predict survival for the high-grade glioma patients and the subgroup with glioblastoma patients. The proteins which correlated most significantly (univariate and multivariate p < 0.05) to survival in the Cox regression analyses were Myc for all high-grade gliomas and FGF2, CA9 and CD44 for the subgroup of proneural gliomas, with FGF2 having a strong negative predictive value for survival. No prognostic signature of the proteins could be found.

Conclusion. FGF2 is a potential prognostic biomarker for proneural glioma patients, and warrants further investigation.

Keyword
Prognostic biomarkers, tissue microarray, immunohistochemistry, FGF2, CA9, CD44
National Category
Cell and Molecular Biology Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-214802 (URN)10.3109/0284186X.2014.951492 (DOI)000350646400012 ()25263081 (PubMedID)
Available from: 2014-01-09 Created: 2014-01-09 Last updated: 2018-01-11Bibliographically approved
Blomberg, C., Nilsson, J., Holgersson, G., Edlund, P., Bergqvist, M., Adwall, L., . . . Bergström, S. (2015). Randomized Trials of Systemic Medically-treated Malignant Mesothelioma: A Systematic Review. Anticancer Research, 35(5), 2493-2501
Open this publication in new window or tab >>Randomized Trials of Systemic Medically-treated Malignant Mesothelioma: A Systematic Review
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2015 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 35, no 5, p. 2493-2501Article, review/survey (Refereed) Published
Abstract [en]

Malignant pleural mesothelioma (MPM) is a rare but aggressive malignancy mainly localized to the pleura. Malignant mesothelioma grows highly invasive into surrounding tissue and has a low tendency to metastasize. The median overall survival (OS) of locally advanced or metastatic disease without treatment is 4-13 months but, during recent years, improvement in survival has been achieved since treatment for patients with mesothelioma has improved with better palliative care, systemic medical treatment, surgery and improved diagnostics methods. The present review aims at describing available data from randomized trials considering systemic medical treatment for this patient category.

Keyword
Malignant mesothelioma, randomized trials, review
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-257356 (URN)000354267200003 ()
Available from: 2015-07-03 Created: 2015-07-01 Last updated: 2017-12-04Bibliographically approved
Elsir, T., Edqvist, P.-H., Carlson, J., Ribom, D., Bergqvist, M., Ekman, S., . . . Smits, A. (2014). A study of embryonic stem cell-related proteins in human astrocytomas: Identification of Nanog as a predictor of survival. International Journal of Cancer, 134(5), 1123-1131
Open this publication in new window or tab >>A study of embryonic stem cell-related proteins in human astrocytomas: Identification of Nanog as a predictor of survival
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2014 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 134, no 5, p. 1123-1131Article in journal (Refereed) Published
Abstract [en]

Recent studies suggest that the regulatory networks controlling the functions of stem cells during development may be abnormally active in human cancers. An embryonic stem cell (ESC) gene signature was found to correlate with a more undifferentiated phenotype of several human cancer types including gliomas, and associated with poor prognosis in breast cancer. In the present study, we used tissue microarrays of 80 low-grade (WHO grade II) and 98 high-grade human gliomas (WHO grade III and IV) to investigate the presence of the ESC-related proteins Nanog, Klf4, Oct4, Sox2 and c-Myc by immunohistochemistry. While similar patterns of co-expressed proteins between low- and high-grade gliomas were present, we found up-regulated protein levels of Nanog, Klf4, Oct4 and Sox2 in high-grade gliomas. Survival analysis by Kaplan-Meier analysis revealed a significant shorter survival in the subgroups of low-grade astrocytomas (n=42) with high levels of Nanog protein (p=0.0067) and of Klf4 protein (p=0.0368), in high-grade astrocytomas (n=85) with high levels of Nanog (p=0.0042), Klf4 (p=0.0447), and c-Myc (p=0.0078) and in glioblastomas only (n=71) with high levels of Nanog (p=0.0422) and of c-Myc (p= 0.0256). In the multivariate model, Nanog was identified as an independent prognostic factor in the subgroups of low-grade astrocytomas (p=0.0039), high-grade astrocytomas (p=0.0124) and glioblastomas only (p=0.0544), together with established clinical variables in these tumors. These findings provide further evidence for the joint regulatory pathways of ESC-related proteins in gliomas and identify Nanog as one of the key players in determining clinical outcome of human astrocytomas.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-207784 (URN)10.1002/ijc.28441 (DOI)000328246700011 ()24037901 (PubMedID)
Note

De två (2) sista författarna delar sistaförfattarskapet.

Available from: 2013-09-18 Created: 2013-09-18 Last updated: 2017-12-06Bibliographically approved
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