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Eklöf, Vincy
Publications (10 of 13) Show all publications
Karling, P., Lundgren, D., Eklöf, V., Palmqvist, R. & Hultdin, J. (2019). Improved monitoring of inflammatory activity in patients with ulcerative colitis by combination of faecal tests for haemoglobin and calprotectin. Scandinavian Journal of Clinical and Laboratory Investigation, 79(5), 341-346
Open this publication in new window or tab >>Improved monitoring of inflammatory activity in patients with ulcerative colitis by combination of faecal tests for haemoglobin and calprotectin
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2019 (English)In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 79, no 5, p. 341-346Article in journal (Refereed) Published
Abstract [en]

Faecal calprotectin (FC) tests and faecal immunological tests (FIT) for haemoglobin have been used to monitor disease activity in patients with ulcerative colitis (UC) but used alone they have some limitation concerning the predictive ability. We aimed to test if an FC test used in combination with FIT could improve the predictive ability. Consecutive out-patients with UC (n = 93) who were admitted for colonoscopy completed a single faecal sample before the start of bowel preparation. A quantitative CALPRO (R) calprotectin ELISA test and a qualitative FIT (cut-off < 40 ng/mL) were analyzed. An estimated Mayo score and a score of histological inflammation was performed blinded to the result of the faecal tests. The sensitivity, specificity, negative predictive value and positive predictive value for endoscopic inflammation (Mayo score > 1) was for FIT 85%, 83%, 96%, 57% and for FC > 186 mu g/g 73%, 87%, 87%, 54%. Corresponding results for FIT*FC > 186 mu g/g (at least one test positive) were 92%, 69%, 97%, 43%. For detecting moderate/severe histological inflammation the results were for FIT 69%, 79%, 92%, 43%, for FC > 75 mu g/g 95%, 62%, 98%, 41%, and for FIT*FC > 75 mu g/g 100%, 60%, 100%, 36%. None of the markers alone or in combination were useful to predict deep remission (Mayo score = 0 and no histological inflammation). We conclude that using the combination of an FC test and FIT shows minor improvement in predictive ability for inflammatory activity and remission in patients with UC.

Place, publisher, year, edition, pages
Taylor & Francis, 2019
Keywords
Faecal calprotectin, faecal immunochemical haemoglobin tests, inflammatory bowel disease, ulcerative colitis
National Category
Other Clinical Medicine
Identifiers
urn:nbn:se:umu:diva-161714 (URN)10.1080/00365513.2019.1622148 (DOI)000473803200001 ()31164011 (PubMedID)
Funder
Västerbotten County Council
Available from: 2019-08-05 Created: 2019-08-05 Last updated: 2020-01-07Bibliographically approved
Lundgren, D., Eklöf, V., Palmqvist, R., Hultdin, J. & Karling, P. (2019). Proton pump inhibitor use is associated with elevated faecal calprotectin levels. A cross-sectional study on subjects referred for colonoscopy. Scandinavian Journal of Gastroenterology, 54(2), 152-157
Open this publication in new window or tab >>Proton pump inhibitor use is associated with elevated faecal calprotectin levels. A cross-sectional study on subjects referred for colonoscopy
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2019 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 54, no 2, p. 152-157Article in journal (Refereed) Published
Abstract [en]

Objectives: Faecal Calprotectin (FC) is a sensitive marker for gut inflammation. However, slightly elevated FC levels are also common in subjects without inflammation. We investigated the association between FC and clinical factors including concomitant use of medical therapy in patients with a normal colonoscopy.Material and methods: Out-patients (n=1263) referred for colonoscopy, performed FC test (CALPRO) the day before the start of bowel preparation. All subjects answered questionnaires that included questions on the present and past health history, concomitant medical treatment and gastrointestinal symptoms (GSRS). A medical record chart review was performed to check for concomitant disease, cause of referral and the result of the colonoscopy including biopsies. Inclusion criteria were a normal colonoscopy. Exclusion criteria were inflammatory bowel disease, colon cancer and high-grade dysplasia.Results: Five hundred ninety subjects fulfilled the inclusion criteria and completed the study. Thirty-six per cent of the subjects had a FC >50 mu g/g. In a logistic regression analysis, age (adjusted OR: 1.051; CI: 1.032-1.071), and the use of proton pump inhibitors (adjusted OR: 3.843; CI: 2.338-6.316), non-steroid anti-inflammatory drugs (adjusted OR: 2.411; CI: 1.162-5.002) and acetylsalicylic acid (adjusted OR: 2.934; CI: 1.085-3.448) were significantly associated with an elevated FC (>50 mu g/g).Conclusions: More than one-third of the patients with a normal colonoscopy performed in clinical routine had a slightly elevated FC level. Our results emphasise the need for attention to age, the use of proton pump inhibitors, non-steroid anti-inflammatory drugs and acetylsalicylic acid in the interpretation of FC tests in clinical practice.

Place, publisher, year, edition, pages
Taylor & Francis, 2019
Keywords
Faecal calprotectin, colonoscopy, non-steroidal inflammatory drugs, proton pump inhibitors
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:umu:diva-160629 (URN)10.1080/00365521.2019.1566493 (DOI)000468463000004 ()30676120 (PubMedID)
Funder
Västerbotten County Council
Available from: 2019-06-20 Created: 2019-06-20 Last updated: 2019-06-20Bibliographically approved
Eklöf, V. (2018). Faecal markers and mutations in diagnosis and prognosis of colorectal cancer. (Licentiate dissertation). Umeå: Umeå university
Open this publication in new window or tab >>Faecal markers and mutations in diagnosis and prognosis of colorectal cancer
2018 (English)Licentiate thesis, comprehensive summary (Other academic)
Alternative title[sv]
Faecesmarkörer och mutationer vid diagnos och colorectal cancer
Place, publisher, year, edition, pages
Umeå: Umeå university, 2018. p. 33
Series
Umeå University medical dissertations, ISSN 0346-6612
National Category
Cancer and Oncology Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-154770 (URN)9789176019269 (ISBN)
Presentation
2018-09-28, NUS, E204, 09:00
Opponent
Supervisors
Available from: 2019-01-03 Created: 2019-01-02 Last updated: 2019-01-03Bibliographically approved
Eklöf, V., Löfgren-Burström, A., Zingmark, C., Edin, S., Larsson, P., Karling, P., . . . Palmqvist, R. (2017). Cancer-associated fecal microbial markers in colorectal cancer detection. International Journal of Cancer, 141(12), 2528-2536
Open this publication in new window or tab >>Cancer-associated fecal microbial markers in colorectal cancer detection
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2017 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 141, no 12, p. 2528-2536Article in journal (Refereed) Published
Abstract [en]

Colorectal cancer (CRC) is the second most common cause of cancer death in the western world. An effective screening program leading to early detection of disease would severely reduce the mortality of CRC. Alterations in the gut microbiota have been linked to CRC, but the potential of microbial markers for use in CRC screening has been largely unstudied. We used a nested case-control study of 238 study subjects to explore the use of microbial markers for clbA+ bacteria harboring the pks pathogenicity island, afa-C+ diffusely adherent Escherichia coli harboring the afa-1 operon, and Fusobacterium nucleatum in stool as potential screening markers for CRC. We found that individual markers for clbA+ bacteria and F. nucleatum were more abundant in stool of patients with CRC, and could predict cancer with a relatively high specificity (81.5% and 76.9%, respectively) and with a sensitivity of 56.4% and 69.2%, respectively. In a combined test of clbA+ bacteria and F. nucleatum, CRC was detected with a specificity of 63.1% and a sensitivity of 84.6%. Our findings support a potential value of microbial factors in stool as putative noninvasive biomarkers for CRC detection. We propose that microbial markers may represent an important future screening strategy for CRC, selecting patients with a "high-risk" microbial pattern to other further diagnostic procedures such as colonoscopy.

Place, publisher, year, edition, pages
John Wiley & Sons, 2017
Keywords
F. nucleatum, clbA, colorectal cancer, gut microbiota, screening, stool
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-142380 (URN)10.1002/ijc.31011 (DOI)000413549900019 ()28833079 (PubMedID)
Available from: 2017-11-29 Created: 2017-11-29 Last updated: 2019-01-02Bibliographically approved
Lundgren, D., Rutegård, J., Eklöf, V., Palmqvist, R. & Karling, P. (2016). Patients with longstanding ulcerative colitis in remission do not have more irritable bowel syndrome-like symptoms than controls. BMC Gastroenterology, 16, Article ID 139.
Open this publication in new window or tab >>Patients with longstanding ulcerative colitis in remission do not have more irritable bowel syndrome-like symptoms than controls
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2016 (English)In: BMC Gastroenterology, ISSN 1471-230X, E-ISSN 1471-230X, Vol. 16, article id 139Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Irritable bowel syndrome (IBS) is more common in patients with ulcerative colitis (UC) than expected. The prevalence of IBS in patients with UC with longstanding disease is not known. We investigated the prevalence of IBS-like symptoms in patients with UC in remission and longstanding disease in comparison to control subjects.

METHODS: Sixty-eight patients with UC and 33 patients with hereditary familiar colon cancer and who underwent colonoscopy surveillance were included. Faecal calprotectin (FC), Gastrointestinal Symptoms Rating Scale-Irritable Bowel Syndrome (GSRS-IBS) and Hospital Anxiety and Depression scale were fulfilled prior to endoscopy. UC in remission was define by steroid-free clinical remission, a Mayo Score ≤ 1 on endoscopy, a FC ≤ 200 μg/g and no significant active inflammation on colon biopsies.

RESULTS: Fifty-five UC patients met the criteria for being in remission. The median disease duration was 17 years. The patients with UC in remission tended to have lower scores on total GSRS-IBS score (6 vs 10.5; p = 0.062) and lower or equal scores on all specific IBS symptoms in comparison to controls. There was a moderate but significant correlation between diarrhoea scores and FC levels (in the span ≤ 200 μg/g) (rs 0.38; p = 0.004) in the UC in remission group.

CONCLUSION: Patients with UC with longstanding disease and in remission do not have more IBS symptoms than controls. In UC patients in remission the FC level in the lower span showed a moderate correlation to symptoms of diarrhoea.

Keywords
Irritable bowel syndrome, Inflammatory bowel disorder, Ulcerative Colitis
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:umu:diva-128590 (URN)10.1186/s12876-016-0553-x (DOI)000388415600001 ()27881072 (PubMedID)
Available from: 2016-12-07 Created: 2016-12-07 Last updated: 2018-06-09Bibliographically approved
Lundberg, I. V., Edin, S., Eklöf, V., Öberg, Å., Palmqvist, R. & Wikberg, M. L. (2016). SOX2 expression is associated with a cancer stem cell state and down-regulation of CDX2 in colorectal cancer. BMC Cancer, 16, Article ID 471.
Open this publication in new window or tab >>SOX2 expression is associated with a cancer stem cell state and down-regulation of CDX2 in colorectal cancer
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2016 (English)In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 16, article id 471Article in journal (Refereed) Published
Abstract [en]

Background: To improve current treatment strategies for patients with aggressive colorectal cancer (CRC), the molecular understanding of subgroups of CRC with poor prognosis is of vast importance. SOX2 positive tumors have been associated with a poor patient outcome, but the functional role of SOX2 in CRC patient prognosis is still unclear. Methods: An in vitro cell culture model expressing SOX2 was used to investigate the functional role of SOX2 in CRC. In vitro findings were verified using RNA from fresh frozen tumor tissue or immunohistochemistry on formalin fixed paraffin embedded (FFPE) tumor tissue from a cohort of 445 CRC patients. Results: Using our in vitro model, we found that SOX2 expressing cells displayed several characteristics of cancer stem cells; such as a decreased proliferative rate, a spheroid growth pattern, and increased expression of stem cell markers CD24 and CD44. Cells expressing SOX2 also showed down-regulated expression of the intestinal epithelial marker CDX2. We next evaluated CDX2 expression in our patient cohort. CDX2 down-regulation was more often found in right sided tumors of high grade and high stage. Furthermore, a decreased expression of CDX2 was closely linked to MSI, CIMP-high as well as BRAF mutated tumors. A decreased expression of CDX2 was also, in a stepwise manner, strongly correlated to a poor patient prognosis. When looking at SOX2 expression in relation to CDX2, we found that SOX2 expressing tumors more often displayed a down-regulated expression of CDX2. In addition, SOX2 expressing tumors with a down-regulated CDX2 expression had a worse patient prognosis compared to those with retained CDX2 expression. Conclusions: Our results indicate that SOX2 expression induces a cellular stem cell state in human CRC with a decreased expression of CDX2. Furthermore, a down-regulated expression of CDX2 results in a poor patient prognosis in CRC and at least part of the prognostic importance of SOX2 is mediated through CDX2 down-regulation.

Keywords
SOX2, CDX2, Colorectal cancer, Prognosis, Cancer stem cell
National Category
Cell and Molecular Biology Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-124507 (URN)10.1186/s12885-016-2509-5 (DOI)000380091600001 ()27411517 (PubMedID)
Available from: 2016-08-19 Created: 2016-08-15 Last updated: 2018-06-07Bibliographically approved
Ling, A., Lundberg, I. V., Eklöf, V., Wikberg, M. L., Öberg, Å., Edin, S. & Palmqvist, R. (2016). The infiltration, and prognostic importance, of Th1 lymphocytes vary in molecular subgroups of colorectal cancer. The Journal of Pathology: Clinical Research, 2(1), 21-31
Open this publication in new window or tab >>The infiltration, and prognostic importance, of Th1 lymphocytes vary in molecular subgroups of colorectal cancer
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2016 (English)In: The Journal of Pathology: Clinical Research, ISSN 2056-4538, Vol. 2, no 1, p. 21-31Article in journal (Refereed) Published
Abstract [en]

Giving strong prognostic information, T-cell infiltration is on the verge of becoming an additional component in the routine clinical setting for classification of colorectal cancer (CRC). With a view to further improving the tools for prognostic evaluation, we have studied how Th1 lymphocyte infiltration correlates with prognosis not only by quantity, but also by subsite, within CRCs with different molecular characteristics (microsatellite instability, CpG island methylator phenotype status, and BRAF and KRAS mutational status). We evaluated the Th1 marker T-bet by immunohistochemistry in 418 archival tumour tissue samples from patients who underwent surgical resection for CRC. We found that a high number of infiltrating Th1 lymphocytes is strongly associated with an improved prognosis in patients with CRC, irrespective of intratumoural subsite, and that both extent of infiltration and patient outcome differ according to molecular subgroup. In brief, microsatellite instability, CpG island methylator phenotype-high and BRAF mutated tumours showed increased infiltration of Th1 lymphocytes, and the most pronounced prognostic effect of Th1 infiltration was found in these tumours. Interestingly, BRAF mutated tumours were found to be more highly infiltrated by Th1 lymphocytes than BRAF wild-type tumours whereas the opposite was seen for KRAS mutated tumours. These differences could be explained at least partly by our finding that BRAF mutated, in contrast to KRAS mutated, CRC cell lines and tumour specimens expressed higher levels of the Th1-attracting chemokine CXCL10, and reduced levels of CCL22 and TGFB1, stimulating Th2/Treg recruitment and polarisation. In conclusion, the strong prognostic importance of Th1 lymphocyte infiltration in CRC was found at all subsites evaluated, and it remained significant in multivariable analyses, indicating that T-bet may be a valuable marker in the clinical setting. Our results also indicate that T-bet is of value when analysed in molecular subgroups of CRC, allowing identification of patients with especially poor prognosis who are in need of extended treatment.

Place, publisher, year, edition, pages
John Wiley & Sons, 2016
Keywords
colorectal cancer, Th1 lymphocytes, intratumoural subsites, molecular subgroups, BRAF, KRAS, prognosis
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-121095 (URN)10.1002/cjp2.31 (DOI)000410840100003 ()27499912 (PubMedID)
Funder
Swedish Cancer Society, CAN2011/839Swedish Research Council, B03488901
Note

Ytterligare finansiärer:

Cancer Research Foundation in Northern Sweden (LP 12-1959 SE)

Syskonen Svenssons Foundation for Medical Research (2014 SE)

Available from: 2016-05-26 Created: 2016-05-26 Last updated: 2018-11-13Bibliographically approved
Lundberg, I. V., Löfgren Burström, A., Edin, S., Eklöf, V., Öberg, Å., Stenling, R., . . . Wikberg, M. L. (2014). SOX2 expression is regulated by BRAF and contributes to poor patient prognosis in colorectal cancer. PLoS ONE, 9(7), Article ID e101957.
Open this publication in new window or tab >>SOX2 expression is regulated by BRAF and contributes to poor patient prognosis in colorectal cancer
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2014 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 7, article id e101957Article in journal (Refereed) Published
Abstract [en]

Sporadic colorectal cancer (CRC) is a common malignancy and also one of the main causes of cancer deaths worldwide. Aberrant expression of the transcription factor SOX2 has recently been observed in several cancer types, but its role in CRC has not been fully elucidated. Here we studied the expression of SOX2 in 441 CRC patients by immunohistochemistry and related the expression to clinicopathological and molecular variables and patient prognosis. SOX2 was expressed in 11% of the tumors and was significantly associated to BRAF(V600E) mutation, but not to KRAS mutations (codon 12 and 13). SOX2 positivity was correlated to poor patient survival, especially in BRAF(V600E) mutated cases. In vitro studies showed that cells expressing the constitutively active BRAF(V600E) had increased SOX2 expression, a finding not found in cells expressing KRAS(G12V). Furthermore, blocking downstream BRAF signalling using a MEK-inhibitor resulted in a decreased expression of SOX2. Since SOX2 overexpression has been correlated to increased migration and invasion, we investigated the SOX2 expression in human CRC liver metastasis and found that a SOX2 positive primary CRC also had SOX2 expression in corresponding liver metastases. Finally we found that cells overexpressing SOX2 in vitro showed enhanced expression of FGFR1, which has been reported to correlate with liver metastasis in CRC. Our novel findings suggest that SOX2 expression is partly regulated by BRAF signalling, and an increased SOX2 expression may promote CRC metastasis and mediate a poor patient prognosis.

Place, publisher, year, edition, pages
Public library of science, 2014
Keywords
island methylator phenotype, transcription factor sox2, dna copy number, gene-expression, microsatellite instability, v600e mutation, lung-cancer, stem-cells, carcinoma, growth
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-91747 (URN)10.1371/journal.pone.0101957 (DOI)000338763800054 ()
Available from: 2014-08-20 Created: 2014-08-15 Last updated: 2018-06-07Bibliographically approved
Eklöf, V., Wikberg, M. L., Edin, S., Dahlin, A. M., Jonsson, B.-A., Öberg, Å., . . . Palmqvist, R. (2013). The prognostic role of KRAS, BRAF, PIK3CA and PTEN in colorectal cancer. British Journal of Cancer, 108(10), 2153-2163
Open this publication in new window or tab >>The prognostic role of KRAS, BRAF, PIK3CA and PTEN in colorectal cancer
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2013 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 108, no 10, p. 2153-2163Article in journal (Refereed) Published
Abstract [en]

Background Mutations in KRAS, BRAF, PIK3CA and PTEN expression have been in focus to predict the effect of epidermal growth factor receptor-blocking therapy in colorectal cancer (CRC). Here, information on these four aberrations was collected and combined to a Quadruple index and used to evaluate the prognostic role of these factors in CRC. Patients We analysed the mutation status in KRAS, BRAF and PIK3CA and PTEN expression in two separate CRC cohorts, Northern Sweden Health Disease Study (NSHDS; n = 197) and Colorectal Cancer in Umea Study (CRUMS; n = 414). A Quadruple index was created, where Quadruple index positivity specifies cases with any aberration in KRAS, BRAF, PIK3CA or PTEN expression. Results Quadruple index positive tumours had a worse prognosis, significant in the NSHDS but not in the CRUMS cohort (NSHDS; P = 0.003 and CRUMS; P = 0.230) in univariate analyses but significance was lost in multivariate analyses. When analysing each gene separately, only BRAF was of prognostic significance in the NSHDS cohort (multivariate HR 2.00, 95% CI: 1.16-3.43) and KRAS was of prognostic significance in the CRUMS cohort (multivariate HR 1.48, 95% CI: 1.02-2.16). Aberrations in PIK3CA and PTEN did not add significant prognostic information. Conclusions Our results suggest that establishment of molecular subgroups based on KRAS and BRAF mutation status is important and should be considered in future prognostic studies in CRC.

Place, publisher, year, edition, pages
Nature Publishing Group, 2013
Keywords
BRAF, colorectal cancer, KRAS, prognosis, Quadruple index
National Category
Cancer and Oncology Cell and Molecular Biology Surgery
Identifiers
urn:nbn:se:umu:diva-76265 (URN)10.1038/bjc.2013.212 (DOI)000319561300030 ()23660947 (PubMedID)
Available from: 2013-07-08 Created: 2013-07-08 Last updated: 2019-01-02Bibliographically approved
Van Guelpen, B., Dahlin, A. M., Hultdin, J., Eklöf, V., Johansson, I., Henriksson, M. L., . . . Palmqvist, R. (2010). One-carbon metabolism and CpG island methylator phenotype status in incident colorectal cancer: a nested case-referent study. Cancer Causes and Control, 21(4), 557-566
Open this publication in new window or tab >>One-carbon metabolism and CpG island methylator phenotype status in incident colorectal cancer: a nested case-referent study
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2010 (English)In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 21, no 4, p. 557-566Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: We related prediagnostic plasma folate, vitamin B12, and total homocysteine concentrations, and the MTHFR 677C>T and 1298A>C polymorphisms, to the risk of colorectal cancer with and without the CpG island methylator phenotype (CIMP).

METHODS: This was a nested case-referent study of 190 cases and double, matched referents from the large, population-based Northern Sweden Health and Disease Study. Using archival tumor tissue, promoter methylation in an eight-gene panel was analyzed by MethyLight.

RESULTS: A reduced risk of CIMP-low/CIMP-high CRC (>/=1 gene methylated) was observed in subjects with very low plasma folate concentrations [multivariate odds ratio 2.96 (95% CI 1.24-7.08) for quintiles two to five versus one (lowest)]. With the exception of a reduced risk in MTHFR 677 TT-homozygotes, none of the other one-carbon variables were associated with the risk of CIMP-low/CIMP-high CRC. For CIMP-negative CRC, only the MTHFR polymorphisms were statistically significantly related to risk, inversely for 677C>T and positively for 1298A>C, but a tendency toward a reduced risk was observed in subjects with an adequate methyl availability, combining the plasma variables [multivariate odds ratio 0.61 (95% CI 0.32-1.15)].

CONCLUSION: Though limited by low power, these findings suggest the possibility of different roles for one-carbon metabolism in different pathways of colorectal tumorigenesis.

Identifiers
urn:nbn:se:umu:diva-31577 (URN)10.1007/s10552-009-9484-y (DOI)000275631900006 ()20012180 (PubMedID)
Available from: 2010-02-11 Created: 2010-02-11 Last updated: 2018-06-08Bibliographically approved
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