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Thunberg, Ulf
Alternative names
Publications (10 of 40) Show all publications
Sorbye, H., Dragomir, A., Sundström, M., Pfeiffer, P., Thunberg, U., Bergfors, M., . . . Glimelius, B. (2015). High BRAF Mutation Frequency and Marked Survival Differences in Subgroups According to KRAS/BRAF Mutation Status and Tumor Tissue Availability in a Prospective Population-Based Metastatic Colorectal Cancer Cohort. PLoS ONE, 10(6), Article ID e0131046.
Open this publication in new window or tab >>High BRAF Mutation Frequency and Marked Survival Differences in Subgroups According to KRAS/BRAF Mutation Status and Tumor Tissue Availability in a Prospective Population-Based Metastatic Colorectal Cancer Cohort
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2015 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 6, article id e0131046Article in journal (Refereed) Published
Abstract [en]

RAS and BRAF mutations impact treatment and prognosis of metastatic colorectal cancer patients (mCRC), but the knowledge is based on trial patients usually not representative for the general cancer population. Patient characteristics, treatment and efficacy according to KRAS, BRAF and MSI status were analyzed in a prospectively collected unselected population-based cohort of 798 non-resectable mCRC patients. The cohort contained many patients with poor performance status (39% PS 2-4) and elderly (37% age>75), groups usually not included in clinical trials. Patients without available tissue micro array (TMA) (42%) had worse prognostic factors and inferior survival (all patients; 7m vs 11m, chemotherapy-treated; 12m vs 17m). The 92 patients (21%) with BRAF mutation had a poor prognosis regardless of microsatellite instability, but receipt of 1-2nd chemotherapy was similar to wildtype BRAF patients. Median survival in this cohort varied from 1 month in BRAF mutated patients not given chemotherapy to 26 months in wildtype KRAS/BRAF patients <75 years in good PS. TMA availability, BRAF mutation and KRAS mutation were all independent prognostic factors for survival. The observed 21% BRAF mutation incidence is higher than the previously and repeatedly reported incidence of 5-12% in mCRC. Screening for BRAF mutations before selection of treatment is relevant for many patients, especially outside clinical trials. A BRAF mutation only partly explained the very poor prognosis of many mCRC patients. Survival in unselected metastatic colorectal cancer patients is extremely variable and subgroups have an extremely short survival compared to trial patients. Patients without available TMA had worse prognostic factors and shorter survival, which questions the total generalizability of present TMA studies and implies that we lack information on the biologically worst mCRC cases. Lack of available tissue is an important underexposed issue which introduces sample bias, and this should be recognized more clearly when conclusions are made from translational mCRC studies.

National Category
Cancer and Oncology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-260642 (URN)10.1371/journal.pone.0131046 (DOI)000358150400074 ()26121270 (PubMedID)
Funder
Swedish Cancer Society
Note

Funding: Norwegian Cancer Society, Danish Cancer Society, Stockholm Cancer Society 

Available from: 2015-08-21 Created: 2015-08-21 Last updated: 2019-04-02Bibliographically approved
Kinch, A., Cavelier, L., Bengtsson, M., Baecklund, E., Enblad, G., Backlin, C., . . . Pauksens, K. (2014). Donor or Recipient Origin of Posttransplant Lymphoproliferative Disorders Following Solid Organ Transplantation. American Journal of Transplantation, 14(12), 2838-2845
Open this publication in new window or tab >>Donor or Recipient Origin of Posttransplant Lymphoproliferative Disorders Following Solid Organ Transplantation
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2014 (English)In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 14, no 12, p. 2838-2845Article in journal (Refereed) Published
Abstract [en]

Previous studies of donor or recipient origin of posttransplant lymphoproliferative disorders (PTLDs) following solid organ transplantation (SOT) have either been small or with selected patient groups. We studied tumor origin in a population-based cohort of 93 patients with PTLD following SOT. Tumor origin of PTLD tissue was analyzed by fluorescence in situ hybridization of the sex chromosomes in cases of sex mismatch between donor and recipient (n=41), or HLA genotyping in cases of identical sex but different HLA type (n=52). Tumor origin of PTLD could be determined in 67 of the 93 cases. All 67 PTLDs were of recipient origin. They were found in recipients of kidney (n=38), liver (n=12), heart (n=10) and lung (n=7). The most common recipient-derived lymphomas were monomorphic B-cell PTLDs (n=45), monomorphic T cell PTLDs (n=9), indolent lymphomas (n=6), and polymorphic PTLD (n=4). Half of the recipient-derived PTLDs were Epstein–Barr virus-positive. Twelve of the recipient-derived PTLDs were located in the grafts: in four cases exclusively and in eight cases in combination with disseminated disease outside the graft. Tumor origin was indeterminable in 26 cases, probably due to low DNA quality. We conclude that the vast majority of PTLDs after SOT was of recipient origin.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2014
Keywords
Posttransplant lymphoproliferative disorders, PTLD, Cell of origin, Donor, Recipient, Solid Organ Transplantation, Graft, Loss of Y chromosome, fluorescence in situ hybridization, HLA typing, Epstein-Barr virus
National Category
Cancer and Oncology
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-234076 (URN)10.1111/ajt.12990 (DOI)000345294300022 ()25307322 (PubMedID)
Available from: 2014-10-14 Created: 2014-10-14 Last updated: 2017-12-05Bibliographically approved
Hedström, G., Thunberg, U., Amini, R.-M., Zainuddin, N., Enblad, G. & Berglund, M. (2014). The MDM2 polymorphism SNP309 is associated with clinical characteristics and outcome in diffuse large B-cell lymphoma. European Journal of Haematology, 93(6), 500-508
Open this publication in new window or tab >>The MDM2 polymorphism SNP309 is associated with clinical characteristics and outcome in diffuse large B-cell lymphoma
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2014 (English)In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 93, no 6, p. 500-508Article in journal (Refereed) Published
Abstract [en]

Introduction: The murine double minute 2 (MDM2) gene encodes a regulatory protein of the p53 pathway. A single nucleotide polymorphism (T to G change) at position 309 (SNP309) in the promotor region of MDM2 affects the transcription activity of MDM2 and has been found to be a negative prognostic marker in several cancers. Patients and methods: In this study, the MDM2 SNP309 polymorphism was analysed in 201 patients with diffuse large B-cell lymphoma and analysed in relation to clinical characteristics and prognosis. Results: Patients homozygous for SNP309T had a significantly longer overall survival, lymphoma-specific survival and disease-free survival (P = 0.002; 0.004 and 0.006 respectively) compared to patients carrying a G allele. The longer overall survival was seen in the subgroup of patients not treated with Rituximab, however, not for Rituximab-treated patients (P = 0.01 and 0.2 respectively). The group homozygous for the T allele also had lower age at diagnosis, a tendency towards lower aaIPI and a significantly lower proportion of patients with p53 aberrations compared to the group including at least one G allele. However, the survival differences persisted even after removal of cases with known p53 aberrations from the analysis. Conclusion: Polymorphism in MDM2 SNP309 could be correlated to some clinical characteristics and for patients not treated with immunotherapy, a G allele was correlated to poor survival, whereas no survival differences were found for patients treated with Rituximab. Herewith, we provide additional information about Diffuse large B-cell Lymphoma (DLBCL) biology and highlight the importance of evaluation of molecular markers in relation to treatment.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-219350 (URN)10.1111/ejh.12388 (DOI)000345302700006 ()24889555 (PubMedID)
Available from: 2014-02-27 Created: 2014-02-27 Last updated: 2017-12-05Bibliographically approved
Berglund, M., Hedström, G., Amini, R.-M., Enblad, G. & Thunberg, U. (2013). High expression of microRNA-200c predicts poor clinical outcome in diffuse large B-cell lymphoma. Oncology Reports, 29(2), 720-724
Open this publication in new window or tab >>High expression of microRNA-200c predicts poor clinical outcome in diffuse large B-cell lymphoma
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2013 (English)In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 29, no 2, p. 720-724Article in journal (Refereed) Published
Abstract [en]

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of B-cell lymphomas. A new and important tool for understanding the biology and clinical course of DLBCL is microRNA expression. This study presents microRNA-200c expression data from 61 DLBCL patients treated with CHOP or R-CHOP. Patients with high microRNA-200c expression had a median survival of 20.3 months and a significantly shorter overall survival (P=0.019) compared to patients with low microRNA-200c expression, who had a median survival of 35.8 months. We also found that patients treated with R-CHOP only and displaying high microRNA-200c expression had a significantly shorter overall survival compared to patients with low microRNA-200c expression, where all patients were still alive at the time of the last follow-up (P=0.0036). Lastly, we found that patients with high microRNA-200c expression had a significantly shorter time from initial diagnosis to the first relapse compared to patients with low microRNA-200c expression (P=0.0001). To our knowledge, this is the first study showing that the expression of microRNA-200c affects the clinical outcome of DLBCL patients, and that microRNA-200c is involved in the biology of DLBCL development, although larger studies are necessary to confirm this. Further investigations may also help to elucidate the biological role of microRNA-200c in DLBCL.

Keywords
Diffuse large B-cell lymphoma, microRNA-200c, Prognosis
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-194853 (URN)10.3892/or.2012.2173 (DOI)000313605100043 ()
Available from: 2013-02-20 Created: 2013-02-19 Last updated: 2017-12-06Bibliographically approved
Berglund, M., Amini, R.-M., Enblad, G. & Thunberg, U. (2013). Is the rs10484561 SNP responsible for differences in age at diagnosis, transformation and death of patients with follicular lymphoma?. International Journal of Hematologic Oncology, 2(5), 391-396
Open this publication in new window or tab >>Is the rs10484561 SNP responsible for differences in age at diagnosis, transformation and death of patients with follicular lymphoma?
2013 (English)In: International Journal of Hematologic Oncology, ISSN 2045-1407, Vol. 2, no 5, p. 391-396Article, review/survey (Refereed) Published
Abstract [en]

Aim:

To analyze follicular lymphoma (FL) patients by determining the genotype at SNP rs10484561 (T or G) and comparing the polymorphism with overall survival, time to transformation, time from transformation to death, and age both dependently and independently of gender.

Materials & methods:A total of 94 patients with FL diagnosed between 1970 and 2000 from a Swedish population were analyzed by PCR–restriction fragment length polymorphism to determine genotypes for rs10484561.

Results:

We found that women with FL and the TT genotype of SNP rs10484561 were older at diagnosis, transformation and when they died (p = 0.03, 0.01 and 0.02, respectively) and had a significantly shorter overall survival (p = 0.04) compared with women with the TG or GG genotypes.

Conclusion:

It is possible that the SNP rs10484561 polymorphism is responsible for differences in age at diagnosis, transformation and death for patients with follicular lymphoma, particularly in women.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-220202 (URN)10.2217/ijh.13.48 (DOI)
Available from: 2014-03-12 Created: 2014-03-12 Last updated: 2014-03-12Bibliographically approved
Hedström, G., Thunberg, U., Berglund, M., Simonsson, M., Amini, R.-M. & Enblad, G. (2013). Low expression of microRNA-129-5p predicts poor clinical outcome in diffuse large B cell lymphoma (DLBCL). International Journal of Hematology, 97(4), 465-471
Open this publication in new window or tab >>Low expression of microRNA-129-5p predicts poor clinical outcome in diffuse large B cell lymphoma (DLBCL)
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2013 (English)In: International Journal of Hematology, ISSN 0925-5710, E-ISSN 1865-3774, Vol. 97, no 4, p. 465-471Article in journal (Refereed) Published
Abstract [en]

Diffuse large B cell lymphoma (DLBCL) is a heterogeneous group of B cell lymphomas. MicroRNA expression provides a new and interesting tool for understanding the biology and clinical course of DLBCL. The present study presents microRNA-129-5p expression data from DLBCL patients treated with CHOP or R-CHOP. Patients with low microRNA-129-5p expression had a median survival of 23 months and a significantly shorter overall survival (P = 0.0042) compared to patients with high microRNA-129-5p expression, who had a median survival of 58 months. We also found that patients treated with R-CHOP only and displaying low microRNA-129-5p expression had a significantly shorter overall survival compared to patients with high microRNA-129-5p expression; all such patients were still alive at the time of last follow-up (P = 0.043). No significant difference was found among microRNA-129-5p expression in tumor tissue, the tissue surrounding the tumor, and normal controls. To our knowledge, this is the first report to show that the expression of microRNA-129-5p can affect the clinical outcome of DLBCL patients and that microRNA-129-5p may be involved in the biology of DLBCL development, although larger studies are necessary to confirm this. Further investigations may also help to elucidate the biological role of microRNA-129-5p in DLBCL.

Keywords
DLBCL, microRNA-129-5p, Prognosis
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-200079 (URN)10.1007/s12185-013-1303-2 (DOI)000317475500005 ()
Available from: 2013-05-23 Created: 2013-05-20 Last updated: 2017-12-06Bibliographically approved
Cederblad, L., Thunberg, U., Engström, M., Castro, J., Rutqvist, L. E. & Laytragoon-Lewin, N. (2013). The Combined Effects of Single-Nucleotide Polymorphisms, Tobacco Products, and Ethanol on Normal Resting Blood Mononuclear Cells. Nicotine & tobacco research, 15(5), 890-895
Open this publication in new window or tab >>The Combined Effects of Single-Nucleotide Polymorphisms, Tobacco Products, and Ethanol on Normal Resting Blood Mononuclear Cells
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2013 (English)In: Nicotine & tobacco research, ISSN 1462-2203, E-ISSN 1469-994X, Vol. 15, no 5, p. 890-895Article in journal (Refereed) Published
Abstract [en]

Introduction: Tobacco and ethanol consumption are crucial factors in the development of various diseases including cancer. In this investigation, we evaluated the combined effects of a number of single nucleotide polymorphisms (SNPs), with ethanol and tobacco products on healthy individuals. Methods: Pure nicotine, cigarette smoke extract, and Swedish snuff (snus) extract were used. The effects were examined by means of in vitro cell cycle progression and cell death of peripheral blood mononuclear cells (PBMCs) obtained from healthy donors. Results: After 3 days, in vitro, resting PBMCs entered the S and G2 stage in the presence of 100 mu M nicotine. The PBMCs only proceeded to S stage, in the presence of 0.2% ethanol. The nicotine- and ethanol-induced normal cell cycle progression correlated to a number of SNPs in the IL12RB2, Rad 52, XRCC2, P53, CCND3, and ABCA1 genes. Certain SNPs in Caspases 8, IL12RB2, Rad 52, MMP2, and MDM2 genes appeared to significantly influence the effects of EtOH-, snus-, and snus + EtOH-induced cell death. Importantly, the highest degree of cell death was observed in the presence of smoke + EtOH. The amount of cell death under this treatment condition also correlated to specific SNPs, located in the MDM2, ABCA1, or GASC1 genes. Conclusions: Cigarette smoke in combination with ethanol strongly induced massive cell death. Long-term exposure to smoke and ethanol could provoke chronic inflammation, and this could be the initiation of disease including the development of cancer at various sites.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-200343 (URN)10.1093/ntr/nts207 (DOI)000317796500004 ()
Available from: 2013-05-28 Created: 2013-05-27 Last updated: 2017-12-06Bibliographically approved
Thunberg, U., Enblad, G. & Berglund, M. (2012). Classification of diffuse large B-cell lymphoma by immunohistochemistry demonstrates that elderly patients are more common in the non-GC subgroup and younger patients in the GC subgroup. [Letter to the editor]. Haematologica, 97(2), e3
Open this publication in new window or tab >>Classification of diffuse large B-cell lymphoma by immunohistochemistry demonstrates that elderly patients are more common in the non-GC subgroup and younger patients in the GC subgroup.
2012 (English)In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 97, no 2, p. e3-Article in journal, Letter (Refereed) Published
Keywords
DLBCL, non-germinal, germinal, immunohistochemistry
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-170964 (URN)10.3324/haematol.2011.057240 (DOI)000300766300002 ()22298823 (PubMedID)
Available from: 2012-03-14 Created: 2012-03-14 Last updated: 2017-12-07Bibliographically approved
Ghawanmeh, T., Thunberg, U., Castro, J., Murray, F. & Laytragoon-Lewin, N. (2011). miR-34a Expression, Cell Cycle Arrest and Cell Death of Malignant Mesothelioma Cells upon Treatment with Radiation, Docetaxel or Combination Treatment. Oncology, 81(5-6), 330-335
Open this publication in new window or tab >>miR-34a Expression, Cell Cycle Arrest and Cell Death of Malignant Mesothelioma Cells upon Treatment with Radiation, Docetaxel or Combination Treatment
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2011 (English)In: Oncology, ISSN 0030-2414, E-ISSN 1423-0232, Vol. 81, no 5-6, p. 330-335Article in journal (Refereed) Published
Abstract [en]

Objective: Malignant mesothelioma (MM) is a highly aggressive tumour related to asbestos exposure. Histopathologically, the tumour is classified as epithelial, sarcomatoid or biphasic. To date, MM is still an incurable disease.

Methods: To evaluate treatment strategies on MM cells, the effects of radiotherapy, docetaxel or a combination of both on MM cells derived from the sarcomatoid type ZL34 and the epithelial type M28K were investigated. The TP53 gene, micro-RNA expression, cell cycle distribution and cell death were assessed as indicators of treatment effects.

Results: Despite the normal TP53 gene sequences in these cell lines, radiation-induced miR-34a expression was detected only in the M28K cells. Increasing G0/G1 cell numbers were detected in irradiated M28K and ZL34 cells. There was more radiation-induced cell death in M28K compared to ZL34 cells. The highest degree of cell cycle arrest at G2 and cell death in both cell types was obtained in the presence of docetaxel. The combination of docetaxel and radiation did not show any additive effects on miR-34a expression, cell cycle arrest or cell death in either the M28K or ZL34 cells.

Conclusion: Microtubule formation and other related functions by docetaxel might be the most suitable treatment modulation in both sarcomatoid and epithelial types of MM.

Keywords
Malignant mesothelioma, Docetaxel, Radiation, p53, miR-34a, Cell cycle, Cell death
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-170965 (URN)10.1159/000334237 (DOI)000300098300008 ()22237142 (PubMedID)
Available from: 2012-03-14 Created: 2012-03-14 Last updated: 2017-12-07Bibliographically approved
Berglund, M., Enblad, G. & Thunberg, U. (2011). SNP rs6457327 is a predictor for overall survival in follicular lymphoma as well as survival after transformation [Letter to the editor]. Blood, 118(16), 4489-4489
Open this publication in new window or tab >>SNP rs6457327 is a predictor for overall survival in follicular lymphoma as well as survival after transformation
2011 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 118, no 16, p. 4489-4489Article in journal, Letter (Refereed) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-162100 (URN)10.1182/blood-2011-06-362921 (DOI)000296286500032 ()
Available from: 2011-11-24 Created: 2011-11-24 Last updated: 2017-12-08Bibliographically approved
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