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Dimberg, Jan
Publications (10 of 51) Show all publications
Olsen, R. S., Dimberg, J., Geffers, R. & Wågsäter, D. (2019). Possible role and therapeutic target of PDGF-D signalling in colorectal cancer. Cancer Investigation, 37(2), 99-112
Open this publication in new window or tab >>Possible role and therapeutic target of PDGF-D signalling in colorectal cancer
2019 (English)In: Cancer Investigation, ISSN 0735-7907, E-ISSN 1532-4192, Vol. 37, no 2, p. 99-112Article in journal (Refereed) Published
Abstract [en]

Platelet-derived growth factor D (PDGF-D) has been shown to mediate cellular processes of importance in cancer progression. This study aimed to investigate the expression and putative involvement of PDGF-D signaling in colorectal carcinogenesis. PDGF-D was expressed in vascular endothelial cells in tumor and normal tissues. PDGF-D stimulation of cells altered genes of importance in carcinogenic processes. In addition, PDGF-D increased the proliferation rate while imatinib inhibited these effects. PDGF-D and its PDGF receptor beta (PDGFR-β) are expressed in colorectal cancer and blockage of PDGF-D/PDGFR-β signaling using tyrosine kinase inhibitors, such as imatinib, might be important in inhibiting tumor-promoting actions.

Place, publisher, year, edition, pages
Taylor & Francis, 2019
Keywords
Angiogenesis, Colorectal cancer, Imatinib, PDGF-D, Proliferation
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:hj:diva-43312 (URN)10.1080/07357907.2019.1576191 (DOI)000462343500005 ()30836770 (PubMedID)2-s2.0-85062496184 (Scopus ID);HHJBiomedicinIS (Local ID);HHJBiomedicinIS (Archive number);HHJBiomedicinIS (OAI)
Available from: 2019-03-11 Created: 2019-03-11 Last updated: 2019-04-11Bibliographically approved
Shamoun, L., Skarstedt, M., Andersson, R. E., Wågsäter, D. & Dimberg, J. (2018). Association study on IL-4, IL-4Rα and IL-13 genetic polymorphisms in Swedish patients with colorectal cancer. Clinica Chimica Acta, 487, 101-106
Open this publication in new window or tab >>Association study on IL-4, IL-4Rα and IL-13 genetic polymorphisms in Swedish patients with colorectal cancer
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2018 (English)In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 487, p. 101-106Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Interleukin 4 (IL-4) and interleukin 13 (IL-13) are anti-inflammatory and immunomodulatory cytokines which share a common cellular receptor IL4Rα and are involved in the same signaling pathways. Our purpose was to assess whether genetic variants within IL-4, IL-13 and IL-4Rα are associated with the risk or clinical outcome of colorectal cancer (CRC).

METHODS: Three single nucleotide polymorphisms (SNPs) were screened in 466 patients with CRC and 445 healthy controls. The selected SNPs were IL-4 SNP rs2243250, IL-4Rα SNP rs1801275 and IL-13 SNP rs1800925.

RESULTS: We found that the genotype variant T/T in IL-13 gene was associated with a higher risk of CRC. Kaplan-Meier analysis showed that the cancer specific survival differed between C/C and CT + TT for IL-4 SNP. Moreover, the carriers of the T allele were associated with the highest risk of CRC death with a hazard ratio (HR) of 1.57, 95% CI 1.06-2.36, p = .024. The observed effect of the T allele was restricted to stage III patients.

CONCLUSION: Our results indicate IL-13 SNP rs1800925 as a risk factor for CRC and that IL-4 SNP rs2243250 could be a useful prognostic marker in the follow-up and clinical management of patients with CRC especially in stage III disease.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Colorectal cancer, IL-13, IL-4, IL-4Rα, SNP
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:hj:diva-41571 (URN)10.1016/j.cca.2018.09.024 (DOI)000451491300018 ()30227113 (PubMedID)2-s2.0-85053800502 (Scopus ID)
Available from: 2018-09-25 Created: 2018-09-25 Last updated: 2019-02-01Bibliographically approved
Shamoun, L., Kolodziej, B., Andersson, R. E. & Dimberg, J. (2018). Protein expression and genetic variation of IL32 and association with colorectal cancer in Swedish patients. Anticancer Research, 38(1), 321-328
Open this publication in new window or tab >>Protein expression and genetic variation of IL32 and association with colorectal cancer in Swedish patients
2018 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 38, no 1, p. 321-328Article in journal (Refereed) Published
Abstract [en]

Background: Interleukin 32 (IL32) is an intracellular pluripotent cytokine produced by epithelial cells, monocytes, T-lymphocytes and natural killer cells and seems to be involved in the pathogenesis of cancer and inflammatory diseases. Our purpose was to assess the role of protein expression and genetic polymorphisms of IL32 in colorectal cancer (CRC) susceptibility.

Materials and Methods: To gain insight into clinical significance of IL32 in Swedish patients with CRC, using enzyme-linked immunosorbent assay, we determined whether IL32 protein level is altered in CRC tissue (n=75) compared with paired normal tissue and in plasma from patients with CRC (n=94) compared with controls (n=81). The expression of IL32 protein was confirmed by immunohistochemistry (n=73). We used Luminex technology to investigate protein levels of the cytokines IL6, tumor necrosis factor-a (TNFa) and vascular endothelial growth factor (VEGF) to relate these to IL32 levels in CRC tissue. Three single nucleotide polymorphisms (SNPs) (rs28372698, rs12934561, rs4786370) of the IL32 gene have been proposed as modifiers for different diseases. The present study evaluated the susceptibility of patients possessing these SNPs to CRC. Using TaqMan SNP genotyping assays, these SNPs were screened in Swedish patients with CRC (n=465) and healthy controls (n=331).

Results: We found no significant differences in the genotypic frequencies between the patients and healthy controls and no relation to survival for any of the SNPs. However, the SNP rs12934561 was statisticalLY significant associated with older patients. IL32 protein was up-regulated in CRC tissue and related to IL6, TNFa, and VEGF, and seems to be modulated by SNP rs28372698. The IL32 protein level in CRC tissue also reflects both disseminated disease and location. Conclusion. Our results suggest that altered IL32 protein concentrations in CRC tissue and genotypic variants of IL32 are related to disseminated CRC.

Place, publisher, year, edition, pages
International Institute of Anticancer Research, 2018
Keywords
Colorectal cancer, IL32, Protein expression, SNP, interleukin 32, interleukin 6, tumor necrosis factor, vasculotropin, IL32 protein, human, IL6 protein, human, interleukin derivative, tumor marker, vasculotropin A, VEGFA protein, human, adult, aged, Article, cancer growth, cancer staging, cancer susceptibility, comparative study, controlled study, disease free survival, DNA polymorphism, enzyme linked immunosorbent assay, female, follow up, genetic polymorphism, genetic variation, human, human tissue, immunohistochemistry, long term survival, major clinical study, male, priority journal, rectum cancer, single nucleotide polymorphism, survival analysis, upregulation, blood, colorectal tumor, early cancer diagnosis, genetic predisposition, genetics, metabolism, middle aged, pathology, procedures, Sweden, very elderly, Aged, 80 and over, Biomarkers, Tumor, Colorectal Neoplasms, Early Detection of Cancer, Enzyme-Linked Immunosorbent Assay, Genetic Predisposition to Disease, Humans, Interleukin-6, Interleukins, Polymorphism, Single Nucleotide, Tumor Necrosis Factor-alpha, Vascular Endothelial Growth Factor A
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:hj:diva-38510 (URN)10.21873/anticanres.12225 (DOI)000419130100042 ()29277790 (PubMedID)2-s2.0-85039801563 (Scopus ID)
Available from: 2018-01-15 Created: 2018-01-15 Last updated: 2019-02-01Bibliographically approved
Olsen, R. S., Nijm, J., Andersson, R. E., Dimberg, J. & Wågsäter, D. (2017). Circulating inflammatory factors associated with worse long-term prognosis in colorectal cancer. World Journal of Gastroenterology, 23(34), 6212-6219
Open this publication in new window or tab >>Circulating inflammatory factors associated with worse long-term prognosis in colorectal cancer
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2017 (English)In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 23, no 34, p. 6212-6219Article in journal (Refereed) Published
Abstract [en]

AIM: To investigate association of circulating inflammatory factors at the time of colorectal cancer (CRC) surgery with survival.

METHODS: Plasma levels from 174 CRC patients (69 females and 105 men), with median age 70 years (range 29-90), localized in the colon (n = 105) or rectum (n = 69), with stage I (n = 24), stage II (n = 54), stage III (n = 67) and stage IV (n = 29) were measured using commercially available Bio-Plex Pro™ Human Chemokine Panel 40-Plex, including 40 different chemokines, cytokines and interleukins. The prognostic association of each inflammatory factor was analysed as CRC-specific and total mortality.

RESULTS: Out of 174 patients, 66 died during the follow-up, 40 because of CRC specific mortality. High tertile levels of 8 factors were significantly associated with increased CRC-specific mortality, of which CCL1, CCL20, CCL24, CX3CL1, IL-4 and TNF-α remained significant in a multivariate Cox regression analysis. High tertile levels of 14 factors were associated with increased total mortality, of which CCL1, CCL15, CCL20, CX3CL1, CXCL13, IFN-γ, IL-2, IL-4 and IL-10 remained significant after adjustment for clinical covariates. For most of the inflammatory factors the association between higher tertile levels and an increased mortality in general appeared two years after surgery. High tertile levels of TNF-α and CCL24 were exclusively associated with CRC-specific mortality. The distribution of these factors were not associated with TNM stage with exception for CCL20.

CONCLUSION: High plasma levels of inflammatory factors are associated with increased risk of mortality among CRC patients and could be potential biomarkers for revealing prognosis.

Place, publisher, year, edition, pages
Baishideng Publishing Group, 2017
Keywords
Colorectal cancer, Cytokines, Inflammation, Mortality, Plasma, Prognosis
National Category
Gastroenterology and Hepatology Cancer and Oncology
Identifiers
urn:nbn:se:hj:diva-37678 (URN)10.3748/wjg.v23.i34.6212 (DOI)000410751600003 ()28974887 (PubMedID)2-s2.0-85029580861 (Scopus ID)GOA HHJ 2017 (Local ID)GOA HHJ 2017 (Archive number)GOA HHJ 2017 (OAI)
Available from: 2017-10-19 Created: 2017-10-19 Last updated: 2019-06-05Bibliographically approved
Song, N. V., Minh, N. K., Dimberg, J., Matussek, A. & Henningsson, A. J. (2017). Prevalence of cervical infection and genotype distribution of human Papilloma virus among females in Da Nang, Vietnam. Anticancer Research, 37(3), 1243-1247
Open this publication in new window or tab >>Prevalence of cervical infection and genotype distribution of human Papilloma virus among females in Da Nang, Vietnam
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2017 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 37, no 3, p. 1243-1247Article in journal (Refereed) Published
Abstract [en]

Aim: The goal of the present study was to determine the prevalence and distribution of high-risk human papilloma virus (HPV) genotypes in women from two districts in and around Da Nang city, Vietnam.

Materials and Methods: All participants were randomly selected, 200 from the Hai Chau district and 200 from the Son Tra district. The detection and genotyping of HPV were performed by real-time polymerase chain reaction (PCR) technique.

Results: Out of a total of 400 women, we found that 38 (9.5%) were infected with a high-risk HPV genotype, the most prevalent genotypes being 16, 18, 58 and 59. By assessment of the HPV findings in relation to sociodemographic characteristics, we found significant differences between the two study districts and between the age groups, as well as differences associated with occupation and the use of contraceptives.

Conclusion: The proportion of high–risk genotypes other than 16 and 18 was relatively high, and since the HPV genotype distribution is known to vary greatly across populations, the information from this study can be used for planning of screening and vaccination programs in Da Nang.

Place, publisher, year, edition, pages
International Institute of Anticancer Research, 2017
Keywords
Cervical cancer; human papilloma virus; high-risk HPV genotype; prevalence; Vietnam
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:hj:diva-35221 (URN)10.21873/anticanres.11440 (DOI)000397129600037 ()28314288 (PubMedID)2-s2.0-85015964342 (Scopus ID)
Available from: 2017-03-20 Created: 2017-03-20 Last updated: 2017-04-21Bibliographically approved
Gabrielson, M., Vorkapic, E., Folkesson, M., Welander, M., Matussek, A., Dimberg, J., . . . Wågsäter, D. (2016). Altered PPARγ coactivator-1 alpha expression in abdominal aortic aneurysm: Possible effects on mitochondrial biogenesis. Journal of Vascular Research, 53(1-2), 17-26
Open this publication in new window or tab >>Altered PPARγ coactivator-1 alpha expression in abdominal aortic aneurysm: Possible effects on mitochondrial biogenesis
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2016 (English)In: Journal of Vascular Research, ISSN 1018-1172, E-ISSN 1423-0135, Vol. 53, no 1-2, p. 17-26Article in journal (Refereed) Published
Abstract [en]

Introduction: Abdominal aortic aneurysm (AAA) is a complex and deadly vascular disorder. The pathogenesis of AAA includes destruction and phenotypic alterations of the vascular smooth muscle cells (VSMCs) and aortic tissues. PPARγ coactivator-1 alpha (PGC1α) regulates VSMC migration and matrix formation and is a major inducer of mitochondrial biogenesis and function, including oxidative metabolism. Methods: Protein and gene expression of PGC1α and markers for mitochondria biogenesis and cell type-specificity were analysed in AAA aortas from humans and mice and compared against control aortas. Results: Gene expression of PPARGC1A was decreased in human AAA and angiotensin (Ang) II-induced AAA in mice when compared to control vessels. However, high expression of PGC1α was detected in regions of neovascularisation in the adventitia layer. In contrast, the intima/media layer of AAA vessel exhibited defective mitochondrial biogenesis as indicated by low expression of PPARGC1A, VDAC, ATP synthase and citrate synthase. Conclusion: Our results suggest that mitochondrial biogenesis is impaired in AAA in synthetic SMCs in the media, with the exception of newly formed supporting vessels in the adventitia where the mitochondrial markers seem to be intact. To our knowledge, this is the first study investigating PGC1α and mitochondria biogenesis in AAA.

Place, publisher, year, edition, pages
S. Karger, 2016
Keywords
Abdominal aortic aneurysm, Mitochondrial biogenesis, Neovascularisation, PGC1α, Vascular smooth muscle cells
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:hj:diva-31210 (URN)10.1159/000446653 (DOI)000386413400002 ()27344146 (PubMedID)2-s2.0-84976581165 (Scopus ID)
Available from: 2016-08-09 Created: 2016-08-09 Last updated: 2018-02-14Bibliographically approved
Dimberg, J., Skarstedt, M., Slind Olsen, R., Andersson, R. E. & Matussek, A. (2016). Gene polymorphism in DNA repair genes XRCC1 and XRCC6 and association with colorectal cancer in Swedish patients. Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), 124(9), 736-740
Open this publication in new window or tab >>Gene polymorphism in DNA repair genes XRCC1 and XRCC6 and association with colorectal cancer in Swedish patients
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2016 (English)In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 124, no 9, p. 736-740Article in journal (Refereed) Published
Abstract [en]

The DNA repair genes XRCC1 and XRCC6 have been proposed to participate in the pathological process of cancer by modulating the DNA repair capacity. This study evaluated the susceptibility of the single-nucleotide polymorphisms (SNPs) XRCC1 (rs25487, G > A) and XRCC6 (rs2267437, C > G) to colorectal cancer (CRC) and their association with clinical parameters in Swedish patients with CRC. Using the TaqMan system, these SNPs were screened in 452 patients and 464 controls. No significant difference in genotype distribution was found between the patients and controls, or any significant association with cancer-specific or disease-free survival in patients. However, we showed that the carriers of allele A in XRCC1 (rs25487, G > A) were connected with a higher risk of disseminated CRC (Odds Ratio = 1.64; 95% Confidence Interval = 1.12–2.41, p = 0.012).

Place, publisher, year, edition, pages
John Wiley & Sons, 2016
Keywords
DNA repair; XRCC1; XRCC6; Single-nucleotide polymorphism; colorectal cancer
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:hj:diva-30846 (URN)10.1111/apm.12563 (DOI)000383581700002 ()27328741 (PubMedID)2-s2.0-84983401255 (Scopus ID)
Funder
Futurum - Academy for Health and Care, Jönköping County Council, Sweden
Available from: 2016-06-23 Created: 2016-06-23 Last updated: 2018-04-10Bibliographically approved
Ögren, J., Van Nguyen, S., Dimberg, J. & Matussek, A. (2016). Prevalence of Dientamoeba fragilis, Giardia duodenalis, Entamoeba histolytica/dispar, and Cryptosporidium spp inDa Nang, Vietnam, detected by a multiplex real-time PCR. Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), 124(6), 529-533
Open this publication in new window or tab >>Prevalence of Dientamoeba fragilis, Giardia duodenalis, Entamoeba histolytica/dispar, and Cryptosporidium spp inDa Nang, Vietnam, detected by a multiplex real-time PCR
2016 (English)In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 124, no 6, p. 529-533Article in journal (Refereed) Published
Abstract [en]

We surveyed the prevalence of Dientamoeba fragilis, Giardia duodenalis, Entamoeba histolytica, Entamoeba dispar, and Cryptosporidium spp in individuals with and without gastrointestinal (GI) symptoms residing in and around Da Nang city, Vietnam. Fecal samples were collected from children (n = 100) and adults (n = 80) with GI symptoms and from healthy individuals (n = 88) reporting no GI symptoms. Parasite detection was performed by multiplex real-time PCR. Overall, except for G. duodenalis, we found a low prevalence (<5%) of D. fragilis and E. dispar and no detection of E. histolytica and C. spp in all participants with GI symptoms. Specifically for D. fragilis this contrasts with findings in European populations of children with GI symptoms showing prevalence up to 73%. Moreover, our results indicate that the prevalence of G. duodenalis is higher in patients with GI symptoms compared to asymptomatic individuals and this difference is most obvious in young patients.

Keywords
Dientamoeba fragilis; Giardia duodenalis; Entamoeba histolytica/dispar and Cryptosporidium spp; PCR; prevalence
National Category
Biomedical Laboratory Science/Technology
Identifiers
urn:nbn:se:hj:diva-29869 (URN)10.1111/apm.12535 (DOI)000376602800013 ()27102222 (PubMedID)2-s2.0-84983021800 (Scopus ID)HHJBiomedicinIS (Local ID)HHJBiomedicinIS (Archive number)HHJBiomedicinIS (OAI)
External cooperation:
Available from: 2016-05-04 Created: 2016-05-04 Last updated: 2017-11-30Bibliographically approved
Dimberg, J., Thai, T. H., Skarstedt, M., Löfgren, S., Zar, N. & Matussek, A. (2014). Novel and Differential Accumulation of Mitochondrial DNA Deletions in Swedish and Vietnamese Patients with Colorectal Cancer. Anticancer Research, 34(1), 147-152
Open this publication in new window or tab >>Novel and Differential Accumulation of Mitochondrial DNA Deletions in Swedish and Vietnamese Patients with Colorectal Cancer
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2014 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 34, no 1, p. 147-152Article in journal (Refereed) Published
Abstract [en]

Background: Mitochondrial DNA (mtDNA) has been proposed to be involved in carcinogenesis and aging. The mtDNA 4977 bp deletion is one of the most frequently observed mtDNA mutations in human tissues and may play a role in colorectal cancer (CRC). In the present study, we aimed to evaluate the frequency of mtDNA 4977 bp deletion in CRC tissues and its association with clinical factors. Patients and Methods: We determined the presence of the 4977 bp common deletion in cancer and normal paired tissue samples from 105 Swedish and 88 Vietnamese patients with CRC using polymerase chain reaction (PCR) assays. Results: The mtDNA 4977 bp deletion was shown to be significantly more frequent in normal tissues in comparison with paired cancer tissues in both Swedish and Vietnamese patients. The 4977 bp common deletion was significantly more frequent in cancer tissues of the Vietnamese patients compared to the Swedish patients, and in Vietnamese cancer tissues, the 4977 bp deletion was significantly over represented in those with localized disease compared to those with disseminated disease. Moreover, we detected nine novel mtDNA deletions and found a significantly higher rate of these in CRC tissues in Swedish in comparison to Vietnamese patients. Conclusion: The mtDNA 4977 bp deletion seems to have an impact on the clinical outcome of CRC in Vietnamese patients, that the Swedish patients accumulate more of the detected novel deletions in CRC tissue compared to Vietnamese patients probably indicates divergent mechanisms in colorectal carcinogenesis.

Keywords
Colorectal cancer; mitochondrial DNA; mtDNA deletion
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:hj:diva-23003 (URN)000329765300016 ()24403455 (PubMedID)2-s2.0-84897027811 (Scopus ID)HHJÖvrigtIS (Local ID)HHJÖvrigtIS (Archive number)HHJÖvrigtIS (OAI)
Available from: 2014-01-08 Created: 2014-01-08 Last updated: 2017-12-06Bibliographically approved
Dimberg, J., Slind Olsen, R., Skarstedt, M., Löfgren, S., Zar, N. & Matussek, A. (2014). Polymorphism of the p38 beta gene in patients with colorectal cancer. Oncology Letters, 8, 1093-1095
Open this publication in new window or tab >>Polymorphism of the p38 beta gene in patients with colorectal cancer
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2014 (English)In: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 8, p. 1093-1095Article in journal (Refereed) Published
Abstract [en]

The p38 mitogen‑activated protein kinase (MAPK) signaling pathways have been proposed to participate in the pathological process of cancer by affecting inflammation, proliferation, metastasis and cell survival. A single nucleotide polymorphism (SNP; rs2235356, ‑1628A→G) in the promoter region of the p38β gene has been proposed as a genetic modifier for colorectal cancer (CRC) in a Chinese population. The present study evaluated the susceptibility of patients possessing this SNP to CRC, in addition to determining its association with clinical parameters in Swedish patients with CRC. Using the LightSNiP genotyping assay, this SNP was screened in 389 patients with CRC and 517 control subjects. No significant difference in the genotype distribution or in the allelic frequencies was identified between the two groups nor was any association identified with the clinical parameters. These findings indicate that the ‑1628A→G polymorphism of the p38β gene is not significantly associated with a susceptibility to CRC in a Swedish population.

Keywords
p38β, promoter region, single nucleotide polymorphism, colorectal cancer
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:hj:diva-24249 (URN)10.3892/ol.2014.2315 (DOI)000340854600024 ()
Available from: 2014-07-16 Created: 2014-07-16 Last updated: 2017-12-05Bibliographically approved
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