Solveig Norheim Andersen

• Alsøe, Lene; Brackmann, Stephan Andreas; Liu, Yan; Wennerström, Anna Berit; Esbensen, Qin Ying & Kalyanasundaram, Sumana [Show all 10 contributors for this article] (2026). The Role of Nuclear APOBEC Enzymes in Neoplastic Progression of Ulcerative Colitis. Clinical and Experimental Gastroenterology. 19. doi: 10.2147/CEG.S588161. Full text in Research Archive Show summary

  Aberrant expression of the cytidine DNA deaminase AID in enterocytes within inflamed mucosa in ulcerative colitis (UC) patients has been proposed to be involved in progression of UC to colitis-associated colorectal cancer (CA-CRC). Here, we followed the expression of AID and other nuclear cytidine DNA deaminases of the APOBEC family through several stages of progression of UC in a CA-CRC case (UC progressor) and in a cohort of UC progressors and non-progressors. In inflamed and high-grade dysplastic mucosa, AICDA and APOBEC1 mRNAs, but not APOBEC3-family enzyme mRNAs, were overexpressed compared to non-inflamed tissue. Immunohistochemical staining did not show expression of AID or APOBEC3 enzymes in the enterocytes, neither in specimens from the CA-CRC case nor in biopsies from the progressor and non-progressor cohort. APOBEC1 was highly expressed in the enterocytes throughout the colorectum from the CA-CRC case and in most biopsies examined from the progressor and non-progressor cohort. The expression was not correlated with the histology of the mucosa or the progression status of the patients. In the CA-CRC case, we identified AID- and APOBEC3-associated mutation signatures in inflamed, high-grade dysplasia and cancer genomes. In conclusion, our findings suggest that AID or other nuclear APOBECs are unlikely to drive the progression of UC to CA-CRC late during course of UC. However, we cannot exclude the possibility that bursts of AID and nuclear APOBEC3 activity may contribute to formation of genome instability in early phases of disease development.

• Alsøe, Lene; Brackmann, Stephan Andreas; Lefol, Yohan Pierre; Wennerström, Anna Berit; Liu, Yan & Riques, Rosa Ana [Show all 8 contributors for this article] (2025). Colonic Mucosal Gene Expression Profile in Patients with Neoplastic Progression in Longstanding Ulcerative Colitis. Clinical and Experimental Gastroenterology. 18, p. 215–232. doi: 10.2147/ceg.s528854. Full text in Research Archive
• Schandiz, Hossein Khalkhali; Farkas, Lorant; Park, Daehoon; Liu, Yan; Andersen, Solveig Norheim & Sauer, Torill [Show all 7 contributors for this article] (2025). High Ki67 expression, HER2 overexpression, and low progesterone receptor levels in high-grade DCIS: significant associations with clinical practice implications. Frontiers in Oncology. 15. doi: 10.3389/fonc.2025.1467664. Full text in Research Archive Show summary

  Simple summary: We investigated the role of Ki67, a ubiquitous marker in cancer, within the context of ductal carcinoma in situ (DCIS), a precursor of invasive breast cancer. Through rigorous analysis of histopathological and immunopathological samples from a substantial cohort, this study revealed robust correlations between heightened Ki67 expression, diminished progesterone (PR) levels, and HER2 overexpression, indicative of aggressive DCIS phenotypes. These findings offer novel insights into the surrogate immunomolecular subtyping landscape of DCIS, potentially refining risk stratification and therapeutic approaches. This elucidation underscores the translational significance of Ki67 as a prognostic and predictive biomarker in DCIS, with implications for personalized treatment paradigms and patient outcomes. Background: The Ki67 proliferation index is widely used in various tumors, including invasive breast carcinoma (IBC). However, its prognostic utility is often constrained by technical complexity. Its diagnostic and clinical significance in ductal carcinoma in situ (DCIS) remains uncertain. We studied Ki67 immunohistochemistry interobserver diagnostic agreement at different cutoff values in high-grade DCIS. Additionally, we investigated the associations between Ki67 expression, PR levels, and human epidermal growth factor receptor 2 (HER2) in high-grade DCIS among various subtypes (Luminal (Lum) A, LumB HER2-, LumB HER2+, HER2-enriched, and triple-negative)). Methods: Using histopathological specimens from 484 patients diagnosed with DCIS between 1996 and 2018, we implemented the 2013 St. Gallen recommendations for surrogate immunomolecular subtyping of IBC. Subtypes were classified, and the Ki67 interobserver diagnostic agreement between Counting Pathologist 1 (CP1) and CP2 was calculated using Cohen’s kappa coefficient at various cutoff values. Results: The Cohen’s kappa coefficient for interobserver agreement between CP1 and CP2 was κ = 0.586, indicating moderate agreement. Ki67 levels varied significantly among subtypes (p < 0.0001), with a median Ki67% being higher in cases with invasive components (p = 0.0351). Low PR combined with high Ki67% was significantly associated with HER2 overexpression (p = 0.0107). Conclusions: Interobserver agreement for the Ki67 count was moderate. Ki67 expression showed considerable variability in high-grade DCIS. Low PR levels combined with high Ki67 expression were linked to HER2 overexpression, showing possible clinical implications for identifying high-risk DCIS.

• Schandiz, Hossein Khalkhali; Farkas, Lorant; Park, Daehoon; Liu, Yan; Andersen, Solveig Norheim & Geisler, Jürgen [Show all 7 contributors for this article] (2024). Low progesterone receptor levels in high-grade DCIS correlate with HER2 upregulation and the presence of invasive components. Frontiers in Oncology. 14:1347166, p. 1–10. doi: 10.3389/fonc.2024.1347166. Full text in Research Archive Show summary

  Objective In this study, we investigated pivotal molecular markers in human high-grade breast ductal carcinoma in situ (DCIS). Expression status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth receptor 2 (HER2) was measured among various subtypes (Luminal (Lum) A, LumB HER2-, LumB HER2+, HER2-enriched and triple-negative). Methods In total, 357 DCIS cases were classified into respective subtypes, according to the 2013 St. Gallen guidelines. Each subtype was categorized into three subcategories: “Pure” (those without an invasive component), “W/invasive” (those with an invasive component), and “All” (the entire group of the given subtype). ER and PR expression were registered as intervals. Equivocal HER2 immunohistochemistry (IHC) cases (2+) were further investigated using dual-color in situ hybridization. Results The majority of patients (71%) were over the age of 50. We discovered no significant differences in the proportion of age between the “Pure” and “W/invasive” groups. There was no significant difference in ER/PR expression between “Pure” luminal subtypes of DCIS and “W/invasive” cases. We compared the HER2 IHC scores of “0”, “1+”, and “2+” among LumA and LumB HER2 subtypes and identified no statistically significant differences between “Pure” and “W/invasive” (p = 0.603). ER and PR expression ≥ 50% cutoff value was present in > 90% of all LumA cases. The incidences of cases with ER expression at cutoff values of < 10% and ≥ 50% in LumA were significantly different compared to other luminal subtypes (p < 0.0001). The proportion of cases with PR expression < 20% showed significant differences in the various luminal subtypes. In luminal B subtypes, low PR expression (< 20%) was significantly associated with both strong HER2 expression (3+) and the presence of an invasive component (p = 0.0001 and p = 0.0365, respectively). Conclusions ER and PR expression at ≥ 50% cutoff values were found in more than 90% of LumA cases. Samples with ER < 10% and ≥ 50% in LumA were significantly different compared to other luminal subtypes (p < 0.0001). Low PR expression in high-grade DCIS was strongly associated with HER2 overexpression (3+) and an invasive component (p = 0.0001 and p = 0.0365, respectively).

• Singh, Banipal Gurpreet; Stimec, Bojan Vladimir; Andersen, Solveig Norheim; Edwin, Bjørn von Gohren; Næsgaard, Jens Marius & Benth, Jurate Saltyte [Show all 7 contributors for this article] (2023). Are Metastatic Central Lymph Nodes (D3 volume) in right-sided Colon Cancer a Sign of Systemic Disease? A sub-group Analysis of an Ongoing Multicenter Trial. Annals of Surgery. ISSN 0003-4932. 279(4), p. 648–656. doi: 10.1097/SLA.0000000000006099. Full text in Research Archive Show summary

  Objective: Assess outcomes of patients with right-sided colon cancer with metastases in the D3 volume after personalized surgery. Background: Patients with central lymph node metastasis (D3-PNG) are considered to have a systemic disease with a poor prognosis. A 3-dimensional definition of the dissection volume allows the removal of all central nodes. Methods: D3-PNG includes consecutive patients from an ongoing clinical trial. Patients were stratified into residual disease negative (D3-RDN) and residual disease positive (D3-RDP) groups. D3-RDN was further stratified into four periods to identify a learning curve. A personalized D3 volume (defined through arterial origins and venous confluences) was removed "en bloc" through medial-to-lateral dissection, and the D3 volume of the specimen was analyzed separately. Results: D3-PNG contained 42(26 females, 63.1SD9.9 y) patients, D3-RDN:29(17 females, 63.4SD10.1 y), and D3-RDP:13(9 females, 62.2SD9.7 y). Mean overall survival (OS) days D3-PNG:1230, D3-RDN:1610, D3-RDP:460. Mean disease-free survival (DFS) was D3-PNG:1023, D3-RDN:1461, D3-RDP:74 days. The probability of OS/ DFS in D3-PNG:52.1%/50.2%, D3-RDN:72.9%/73.1%, D3-RDP: 7.7%/0%. There is a significant change in OS/DFS in the D3-RDN from 2011-2013 to 2020-2022(both P=0.046) and from 2014-2016 to 2020-2022 (P=0.028 and P=0.005,respectively). Conclusion: Our results indicate that surgery can achieve survival in most patients with central lymph node metastases by removing a personalized and anatomically defined D3 volume. The extent of mesenterectomy and the quality of surgery are paramount since a learning curve has demonstrated significantly improved survival over time, despite the low number of patients. These results imply a place for the centralization of this patient group, where feasible.

• Luzon, Javier; Thorsen, Yngve; Nogueira, Liebert Parreiras; Andersen, Solveig Norheim; Edwin, Bjørn von Gohren & Haugen, Håvard Jostein [Show all 8 contributors for this article] (2022). Reconstructing topography and extent of injury to the superior mesenteric artery plexus in right colectomy with extended D3 mesenterectomy: a composite multimodal 3-dimensional analysis. Surgical Endoscopy. ISSN 0930-2794. 36(10), p. 7607–7618. doi: 10.1007/s00464-022-09200-2. Full text in Research Archive Show summary

  Background Superior mesenteric artery plexus (SMAP) injury is reported to cause postoperative intractable diarrhea after pancreatic/colonic surgery with extended lymphadenectomy. This study aims to describe the SMAP microanatomy and extent of injury after right colectomy with extended D3 mesenterectomy for cancer. Methods Three groups (I) anatomical dissection, (II) postmortem histology, and (III) surgical specimen histology were included. Nerve count and area were compared between groups II and III and paravascular sheath thickness between groups I and II. 3D models were generated through 3D histology, nanoCT scanning, and finally through 3D printing. Results A total of 21 specimens were included as follows: Group (I): 5 (3 females, 80–93 years), the SMAP is a complex mesh surrounding the superior mesenteric artery (SMA), branching out, following peripheral arteries and intertwining between them, (II): 7 (5 females, 71–86 years), nerve count: 53 ± 12.42 (38–68), and area: 1.84 ± 0.50 mm2 (1.16–2.29), and (III): 9 (5 females, 55–69 years), nerve count: 31.6 ± 6.74 (range 23–43), and area: 0.889 ± 0.45 mm2 (range 0.479–1.668). SMAP transection injury is 59% of nerve count and 48% of nerve area at middle colic artery origin level. The median values of paravascular sheath thickness decreased caudally from 2.05 to 1.04 mm (anatomical dissection) and from 2.65 to 1.17 mm (postmortem histology). 3D histology models present nerve fibers exclusively within the paravascular sheath, and lymph nodes were observed only outside. NanoCT-derived models reveal oblique nerve fiber trajectories with inclinations between 35° and 55°. Two 3D-printed models of the SMAP were also achieved in a 1:2 scale. Conclusion SMAP surrounds the SMA and branches within the paravascular sheath, while bowel lymph nodes and vessels lie outside. Extent of SMAP injury on histological slides (transection only) was 48% nerve area and 59% nerve count. The 35°–55° inclination range of SMAP nerves possibly imply an even larger injury when plexus excision is performed (lymphadenectomy). Reasons for later improvement of bowel function in these patients can lie in the interarterial nerve fibers between SMA branches.

• Singh, Banipal Gurpreet; Stimec, Bojan Vladimir; Andersen, Solveig Norheim; Færden, Arne Engebreth; Edwin, Bjørn von Gohren & Baral, J. [Show all 9 contributors for this article] (2022). Comparing 5-Year Survival Rates Before and After Re-stratification of Stage I–III Right-Sided Colon Cancer Patients by Establishing the Presence/Absence of Occult Tumor Cells and Lymph Node Metastases in the Different Levels of Surgical Dissection. Journal of Gastrointestinal Surgery. ISSN 1091-255X. 26(10), p. 2201–2211. doi: 10.1007/s11605-022-05434-6. Full text in Research Archive Show summary

  To establish the impact of re-stratification on the outcomes of patients (stage I–III right-sided colon cancer) based on the presence/absence of occult tumor cells (OTC) and/or metastatic lymph nodes in the different levels of surgical dissection. Methods Consecutive patients were drawn from a multicenter prospective trial. After surgery, the surgical specimen was divided into the D1/D2 and D3 volumes before being further analyzed separately. All lymph nodes were examined with cytokeratin CAM 5.2 immunohistochemically. Lymph nodes containing metastases and OTC (micrometastases; isolated tumor cells) were identified. Re-stratification was as follows: RS1, stages I/II, no OTC in D1/D2 and D3 volumes; RS2, stages I/II, OTC in D1/D2 and/or D3; RS3, stage III, lymph node metastases in D1/D2, with/without OTC in D3; RS4, stage III, lymph node metastases in D3, with/without OTC in D3. Results Eighty-seven patients (39 men, 68.4 + 9.9 years) were included. The standard stratified (SS) group contained the following: stages I/II (SS1) 57 patients; stage III (SS2) 30 patients. Re-stratified (RS) contained RS1 (38), RS2 (19), RS3 (24), and RS4 (6) patients. Lymph node ratio (OTC) RS2: 0.157 D1/D2; 0.035 D3 and 0.092 complete specimens. Lymph node ratio RS3: 0.113 D1/D2; complete specimen 0.056. Overall survival and disease-free survival were p = 0.875 and p = 0.049 for SS and p = 0.144 and p = 0.001 for RS groups, respectively. Conclusion This re-stratification identifies a patient group with poor prognosis (RS4). Removing this group from SS2 eliminates all the differences in survival between RS2 and RS3 groups. The level of dissection of the affected nodes may have an impact on survival.

• Angelis, Paula De; Dorg, Linda Trobe; Pham, Sean & Andersen, Solveig Norheim (2021). DNA repair protein expression and oxidative/nitrosative stress in ulcerative colitis and sporadic colorectal cancer. Anticancer Research. ISSN 0250-7005. 41(7), p. 3261–3270. doi: 10.21873/anticanres.15112. Full text in Research Archive
• Singh, Banipal Gurpreet; Stimec, Bojan V.; Andersen, Solveig Norheim; Færden, Arne Engebreth; Edwin, Bjørn von Gohren & Baral, Joerg [Show all 8 contributors for this article] (2021). Interactions of occult tumor spread and surgical technique on overall and disease-free survival in patients operated for stage I and II right-sided colon cancer. Journal of Cancer Research and Clinical Oncology. ISSN 0171-5216. 147(12), p. 3535–3543. doi: 10.1007/s00432-021-03773-6. Full text in Research Archive Show summary

  Purpose To determine if “medial to lateral” (ML) dissection with devascularization first is superior to “lateral to medial” (LM) dissection regarding numbers of lymph node micro metastases (MM) and isolated tumor cells (ITC) as well as 5-year disease-free (5YDFS) and 5-year overall survival (5YOS) in stage I/II right-sided colon cancer. Methods Two datasets are used. ML group consists of consecutive stage I/II patients from a prospective trial. LM group is the original dataset from a previous publication. All harvested lymph nodes are examined with monoclonal antibody CAM 5.2 (immunohistochemically). Lymph node harvest and 5YOS/5YDFS were compared between ML/LM groups, stage I/II tumors and MM/ITC presence/absence. Results 117 patients included ML:51, LM:66. MM/ITC positive in ML 37.3% (19/51), LM 31.8% (21/66) p = 0.54. The 5YDFS for patients in ML 70.6% and LM 69.7%, p = 0.99, 5YOS: 74.5% ML and 71.2% LM (p = 0.73). No difference in 5YDFS/5YOS between groups for Stage I/II tumors; however, LM group had an excess of early tumors (16) when compared to ML group, while lymph node harvest was significantly higher in ML group (p < 0.01) 15.1 vs 26.7. 5YDFS and 5YOS stratified by MM/ITC presence/absence was 67.5%/71.4%, p = 0.63, and 75.0%/71.4%, p = 0.72, respectively. Death due to recurrence in MM/ITC positive was significantly higher than MM/ITC negative (p = 0.012). Conclusion Surgical technique does not influence numbers of MM/ITC or 5YDFS/5YOS. Presence of MM/ITC does not affect 5YOS/5YDFS but can be a potential prognostic factor for death due to recurrence. Clinical trial Safe Radical D3 Right Hemicolectomy for Cancer through Preoperative Biphasic Multi-Detector Computed Tomography (MDCT) Angiography” registered at http://clinicaltrials.gov/ct2/show/NCT01351714 .

• Joshi, Sarita; Angelis, Paula De; Zucknick, Manuela; Schjølberg, Aasa Rambæk; Andersen, Solveig Norheim & Clausen, Ole Petter Fraas (2020). Role of the Wnt signaling pathway in keratoacanthoma. Cancer Reports. 3(2), p. 1–11. doi: 10.1002/cnr2.1219. Full text in Research Archive
• Gulati, Rachna Shridhar; Wimalanathan, Thakshani; Andersen, Solveig Norheim; Isaksen, Kjetil; Lagging, Martin & Midgard, Håvard [Show all 8 contributors for this article] (2019). The relationship between IFNL4 genotype and the rate of fibrosis in hepatitis C patients. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 54(9), p. 1172–1175. doi: 10.1080/00365521.2019.1643403. Full text in Research Archive
• Willard, Christer-Daniel; Kjæstad, Erik; Stimec, Bojan; Edwin, Bjørn; Ignjatovic, Dejan & Øresland, Tom [Show all 32 contributors for this article] (2018). Preoperative anatomical road mapping reduces variability of operating time, estimated blood loss, and lymph node yield in right colectomy with extended D3 mesenterectomy for cancer. International Journal of Colorectal Disease. ISSN 0179-1958. 34(1), p. 151–160. doi: 10.1007/s00384-018-3177-5. Full text in Research Archive
• Angelis, Paula De; Schjølberg, Aasa Rambæk; Hughes, Juliana Bentes; Huitfeldt, Henrik; Andersen, Solveig Norheim & Østvold, Anne Carine (2018). Nondysplastic ulcerative colitis has high levels of the homologous recombination repair protein NUCKS1 and low levels of the DNA damage marker gamma-H2AX. Inflammatory Bowel Diseases. ISSN 1078-0998. 24(3), p. 593–600. doi: 10.1093/ibd/izx071. Full text in Research Archive Show summary

  Background The colon and rectum are continuously exposed to oxidative stress that generates reactive oxygen species, which are a major cause of DNA double-strand breaks (DSB). Furthermore, chronic inflammatory diseases such as ulcerative colitis (UC) are characterized by an excess of reactive nitrogen species that can also lead to DNA double-strand breakage and genomic instability. We investigated the expression of the nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) protein in UC and sporadic colorectal cancer (CRC) due to its involvement in both DNA double-strand break repair and inflammatory signaling. Methods NUCKS1 expression and expression of the DNA double-strand break marker gamma-H2AX (γH2AX) were assessed in formalin-fixed, paraffin-embedded UC and CRC patient biopsies using peroxidase immunohistochemistry. Expression levels for both proteins were evaluated together with previously published expression-level data for hTERT and TP53 proteins in the same material. Results Nondysplastic UC lesions had 10-fold lower γH2AX expression and approximately 4-fold higher NUCKS1 expression compared with sporadic CRC, indicating minimal DNA DSB damage and heightened DNA DSB repair in these lesions, respectively. NUCKS1 expression in UC tended to decrease with increasing grades of dysplasia, whereas γH2AX, hTERT, and TP53 expression tended to increase with increasing grades of dysplasia. The highest γH2AX expression was seen in sporadic CRC, indicating considerable DNA DSB damage, whereas the highest NUCKS1 expression and hTERT expression were seen in nondysplastic UC. Conclusions Overall, our data suggest that NUCKS1 may be involved in DNA DSB repair and/or inflammatory signaling in UC, but a more thorough investigation of both pathways in UC is warranted.

• Klepp, Pasquale Catherine; Kisiel, John; Småstuen, Milada Cvancarova; Røseth, Arne; Andersen, Solveig Norheim & Vatn, Morten H [Show all 9 contributors for this article] (2018). Multi-target stool DNA test in the surveillance of inflammatory bowel disease: a cross-sectional cohort study. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 53(3), p. 273–278. doi: 10.1080/00365521.2018.1424935. Full text in Research Archive
• Klepp, Pasquale Catherine; Tollisen, Anita; Røseth, Arne; Småstuen, Milada Cvancarova; Andersen, Solveig Norheim & Vatn, Morten H [Show all 8 contributors for this article] (2018). Real-life chromoendoscopy for dysplasia surveillance in ulcerative colitis. World Journal of Gastroenterology (WJG). ISSN 1007-9327. 24(35), p. 4069–4076. doi: 10.3748/wjg.v24.i35.4069. Full text in Research Archive Show summary

  AIM: To evaluate the use of chromoendoscopy for surveillance of ulcerative colitis in a real-life community hospital setting. METHODS: Patients with extensive ulcerative colitis, having disease duration of more than 8 years and who presented between the years of 1999 to 2013, were offered enrolment in this single cohort prospective study. All participants underwent standard bowel preparation with sodium phosphate and chromoendoscopy. Two expert endoscopists, novice to chromoendoscopy, evaluated each segment of the colon with standard-definition colonoscopes after spray application of 0.4% indigo carmine. All observed lesions were recorded and evaluated before being removed and/or biopsied. In addition, nontargeted biopsies were taken from each segment of the colon. The dysplasia detection rate and dysplasia detection yield were ascertained. RESULTS: A total of 21 neoplastic lesions (2 carcinomas, 4 of high-grade dysplasia and 15 of low-grade dysplasia) and 27 nondysplastic lesions were detected in 16 of the total 67 patients (70% male; median disease duration: 17 years; median age at diagnosis: 25 years; 92% aminosalicylate-treated). The dysplasia detection rate was 10.5% (7/67 patients). The dysplasia detection yield was 20.8% (10/48) for targeted biopsies and 3.5% (11/318) for nontargeted biopsies. The sensitivity and specificity for the macroscopic evaluation of neoplasia using chromoendoscopy were 48% [95% confidence interval (CI): 26%-70%] and 96% (95%CI: 93%-98%), respectively. The positive predictive and negative predictive values were 42% (95%CI: 27%-59%) and 97% (95%CI: 95%-98%), respectively. A total of 19/21 dysplastic lesions were detected in mucosa with histologic inflammation. CONCLUSION: Chromoendoscopy seems to be of value for dysplasia surveillance of ulcerative colitis in a community hospital setting. The yield of non-targeted biopsies is negligible.

• Beitnes, Ann-Christin Røberg; Vikskjold, Florin Berge; Jóhannesdóttir, Gróa Björk; Perminow, Gøri Margrete; Olbjørn, Christine & Andersen, Solveig Norheim [Show all 9 contributors for this article] (2017). Symptoms and mucosal changes stable during rapid increase of pediatric celiac disease in Norway. Journal of Pediatric Gastroenterology and Nutrition - JPGN. ISSN 0277-2116. 64(4), p. 586–591. doi: 10.1097/MPG.0000000000001307. Full text in Research Archive
• Kalanxhi, Ert; Risberg, Karianne; Barua, Imon Shoumitra; Dueland, Svein; Waagene, Stein & Andersen, Solveig Norheim [Show all 11 contributors for this article] (2017). Induction of Apoptosis in Intestinal Toxicity to a Histone Deacetylase Inhibitor in a Phase I Study with Pelvic Radiotherapy. Cancer research and treatment : official journal of Korean Cancer Association. ISSN 1598-2998. 49(2), p. 374–386. doi: 10.4143/crt.2016.080. Full text in Research Archive Show summary

  Purpose When integrating molecularly targeted compounds in radiotherapy, synergistic effects of the systemic agent and radiation may extend the limits of patient tolerance, increasing the demand for understanding the pathophysiological mechanisms of treatment toxicity. In this Pelvic Radiation and Vorinostat (PRAVO) study, we investigated mechanisms of adverse effects in response to the histone deacetylase (HDAC) inhibitor vorinostat (suberoylanilide hydroxamic acid, SAHA) when administered as a potential radiosensitiser. Materials and Methods This phase I study for advanced gastrointestinal carcinoma was conducted in sequential patient cohorts exposed to escalating doses of vorinostat combined with standard-fractionated palliative radiotherapy to pelvic target volumes. Gene expression microarray analysis of the study patient peripheral blood mononuclear cells (PBMC) was followed by functional validation in cultured cell lines and mice treated with SAHA. Results PBMC transcriptional responses to vorinostat, including induction of apoptosis, were confined to the patient cohort reporting dose-limiting intestinal toxicities. At relevant SAHA concentrations, apoptotic features (annexin V staining and caspase 3/7 activation, but not poly-(ADP-ribose)-polymerase cleavage) were observed in cultured intestinal epithelial cells. Moreover, SAHA-treated mice displayed significant weight loss. Conclusion The PRAVO study design implemented a strategy to explore treatment toxicity caused by an HDAC inhibitor when combined with radiotherapy and enabled the identification of apoptosis as a potential mechanism responsible for the dose-limiting effects of vorinostat. To the best of our knowledge, this is the first report deciphering mechanisms of normal tissue adverse effects in response to an HDAC inhibitor within a combined-modality treatment regimen.

• Joshi, Sarita; Schjølberg, Aasa Rambæk; Ekstrøm, Per Olaf; Angelis, Paula De; Zucknick, Manuela & Andersen, Solveig Norheim [Show all 7 contributors for this article] (2016). Tp53/p53 status in keratoacanthomas. Journal of cutaneous pathology. ISSN 0303-6987. 43(7), p. 571–578. doi: 10.1111/cup.12713. Full text in Research Archive
• Thorsen, Yngve; Stimec, Bojan V.; Andersen, Solveig Norheim; Lindstrøm, Jonas Christoffer; Pfeffer, Frank & Øresland, Tom [Show all 8 contributors for this article] (2016). Bowel function and quality of life after superior mesenteric nerve plexus transection in right colectomy with D3 extended mesenterectomy. Techniques in Coloproctology. ISSN 1123-6337. p. 1–9. doi: 10.1007/s10151-016-1466-y. Full text in Research Archive Show summary

  Background: The aim of this study was to ascertain the impact of injury to the superior mesenteric nerve plexus caused by right colectomy with D3 extended mesenterectomy as performed in the prospective multicenter trial: “Safe Radical D3 Right Hemicolectomy for Cancer through Preoperative Biphasic Multi-detector Computed Tomography” in which all soft tissue surrounding the superior mesenteric vessels from the level of the middle colic artery to that of the ileocolic artery was removed. Methods: Bowel function and gastrointestinal quality of life in two consecutive cohorts that underwent right colectomy with and without D3 extended mesenterectomy were compared. Main outcome measures were the Diarrhea Assessment Scale (DAS) and Gastrointestinal Quality of Life Index (GIQLI). The data were collected prospectively through telephone interviews. Results: Forty-nine patients per group, comparable for age, sex, length of bowel resected but with significantly shorter follow-up time in the experimental group, were included. There was no difference in total DAS scores, subscores or additional questions except for higher bowel frequency scores in the D3 group (p = 0.02). Comparison of total GIQLI scores and subscales showed no difference between groups. Regression analysis with correction for confounding factors showed 0.48 lower bowel frequency scores in the D2 group (p = 0.022). Within the D3 group presence of jejunal arteries cranial to the D3 dissection area showed 1.78 lower DAS scores and 0.7 lower bowel frequency scores. Conclusions: Small bowel denervation after right colectomy with D3 extended mesenterectomy leads to increased bowel frequency but does not impact gastrointestinal quality of life. Individual anatomical variants can affect postoperative bowel function differently despite standardized surgery.

• Friis-Ottessen, Mariann; Burum-Auensen, Espen; Schjølberg, Aasa Rambæk; Ekstrøm, Per Olaf; Andersen, Solveig Norheim & Clausen, Ole Petter Fraas [Show all 7 contributors for this article] (2015). TP53/p53 alterations and Aurora A expression in progressor and non-progressor colectomies from patients with longstanding ulcerative colitis. International Journal of Molecular Medicine. ISSN 1107-3756. 35(1), p. 24–30. doi: 10.3892/ijmm.2014.1974. Full text in Research Archive
• Friis-Ottessen, Mariann; Bendix, Laila; Kølvraa, Steen; Andersen, Solveig Norheim; Angelis, Paula De & Clausen, Ole Petter Fraas (2014). Telomere shortening correlates to dysplasia but not to DNA aneuploidy in longstanding ulcerative colitis. BMC Gastroenterology. 14(1). doi: 10.1186/1471-230X-14-8. Full text in Research Archive Show summary

  Background Ulcerative colitis (UC) is a chronic, inflammatory bowel disease which may lead to dysplasia and adenocarcinoma in patients when long-lasting. Short telomeres have been reported in mucosal cells of UC patients. Telomeres are repetitive base sequences capping the ends of linear chromosomes, and protect them from erosion and subsequent wrongful recombination and end-to-end joining during cell division. Short telomeres are associated with the development of chromosomal instability and aneuploidy, the latter being risk factors for development of dysplasia and cancer. Specifically, the abrupt shortening of one or more telomeres to a critical length, rather than bulk shortening of telomeres, seems to be associated with chromosomal instability. Methods We investigated possible associations between dysplasia, aneuploidy and telomere status in a total of eight lesions from each of ten progressors and four nonprogressors suffering from longstanding UC. We have analyzed mean telomere length by qPCR, as well as the amount of ultra-short telomeres by the Universal STELA method. Results An increased amount of ultra-short telomeres, as well as general shortening of mean telomere length are significantly associated with dysplasia in longstanding UC. Furthermore, levels of ultra-short telomeres are also significantly increased in progressors (colons harbouring cancer/dysplasia and/or aneuploidy) compared to nonprogressors (without cancer/dysplasia/aneuploidy), whereas general shortening of telomeres did not show such associations. Conclusions Our data suggest that ultra-short telomeres may be more tightly linked to colorectal carcinogenesis through development of dysplasia in UC than general telomere shortening. Telomere status was not seen to associate with DNA aneuploidy.

• Friis-Ottessen, Mariann; Angelis, Paula De; Schjølberg, Aasa Rambæk; Andersen, Solveig Norheim & Clausen, Ole Petter Fraas (2014). Reduced hTERT protein levels are associated with DNA aneuploidy in the colonic mucosa of patients suffering from longstanding ulcerative colitis. International Journal of Molecular Medicine. ISSN 1107-3756. 33(6), p. 1477–1483. doi: 10.3892/ijmm.2014.1708. Full text in Research Archive
• Færden, Arne Engebret; Sjo, Ole Helmer; Bukholm, Ida Rashida Khan; Andersen, Solveig Norheim; Svindland, Aud & Nesbakken, Arild [Show all 7 contributors for this article] (2011). Lymph Node Micrometastases and Isolated Tumor Cells Influence Survival in Stage I and II Colon Cancer. Diseases of the Colon & Rectum. ISSN 0012-3706. 54(2), p. 200–206. doi: 10.1007/DCR.0b013e3181fd4c7c. Full text in Research Archive
• Sørby, Lise Aagaard; Kleiveland, Charlotte Ramstad; Andersen, Solveig Norheim; Bukholm, Ida Rashida Khan & Jacobsen, Morten (2011). The Endothelin Axis in the Metastatic Process of Colon Carcinoma. Anticancer Research. ISSN 0250-7005. 31(3), p. 861–869. Full text in Research Archive
• Storli, Kristian Eeg; Søndenaa, Karl; Furnes, Bjørg; Leh, Sabine; Nesvik, Idunn & Bru, Tore [Show all 10 contributors for this article] (2011). Improved Lymph Node Harvest from Resected Colon Cancer Specimens Did Not Cause Upstaging from TNM Stage II to III. World Journal of Surgery. ISSN 0364-2313. 35(12), p. 2796–2803. doi: 10.1007/s00268-011-1248-7. Full text in Research Archive
• Brackmann, Stephan; Aamodt, Geir; Andersen, Solveig Norheim; Roald, Borghild; Langmark, Frøydis & Clausen, Ole Petter Fraas [Show all 10 contributors for this article] (2010). Widespread But Not Localized Neoplasia in Inflammatory Bowel Disease Worsens the Prognosis of Colorectal Cancer. Inflammatory Bowel Diseases. ISSN 1078-0998. 16(3), p. 474–481. doi: 10.1002/ibd.21053. Full text in Research Archive
• Aamodt, Rolf; Bondi, Johan Fridtjof; Andersen, Solveig Norheim; Bakka, Arne Olav; Bukholm, Geir & Bukholm, Ida Rashida Khan (2010). The Prognostic Impact of Protein Expression of E-Cadherin-Catenin Complexes Differs between Rectal and Colon Carcinoma. Gastroenterology Research and Practice. ISSN 1687-6121. doi: 10.1155/2010/616023. Full text in Research Archive
• Sørby, Lise Aagaard; Andersen, Solveig Norheim; Bukholm, Ida Rashida Khan & Jacobsen, Morten (2010). Evaluation of suitable reference genes for normalization of real-time reverse transcription PCR analysis in colon cancer. Journal of Experimental and Clinical Cancer Research. ISSN 0392-9078. 29. doi: 10.1186/1756-9966-29-144. Full text in Research Archive Show summary

  Background Real-time reverse transcription PCR (qRT-PCR) is frequently used for gene expression quantification due to its methodological reproducibility and sensitivity. The gene expression is quantified by normalization to one or more reference genes which are presumed stably expressed throughout a given experiment. The aim of this study was to validate a standardized experimental setup to identifying reference genes for normalization of qRT-PCR in the metastatic and non-metastatic colon cancer. Methods In this study, expression of 16 commonly used reference genes was quantified in tumour tissue and individual-matched normal mucosa in 18 non-metastatic colon cancer patients and 20 colon cancer patients with distant metastases using TaqMan Low Density Array (TLDA). The expression stability was determined and compared by means of geNorm and NormFinder. Results Two pairs of genes, HPRT1/PPIA and IPO8/PPIA, were identified to be suitable to normalize gene expression data in metastatic and non-metastatic colon cancer patients, according to geNorm and NormFinder respectively. Conclusion We propose a standardized approach of finding the most suitable reference gene(s) in every qRT-PCR experiment using TLDA.

• Brackmann, Stephan; Aamodt, Geir; Andersen, Solveig Norheim; Roald, Borghild; Langmark, Frøydis & Clausen, Ole Petter Fraas [Show all 10 contributors for this article] (2009). Widespread but not localized neoplasia in inflammatory bowel disease worsens the prognosis of colorectal cancer. Inflammatory Bowel Diseases. ISSN 1078-0998. doi: 10.1002/ibd.21053. Full text in Research Archive
• Brackmann, Stephan; Andersen, Solveig Norheim; Aamodt, Geir; Roald, Borghild; Langmark, Frøydis & Clausen, Ole Petter Fraas [Show all 10 contributors for this article] (2009). Two distinct groups of colorectal cancer in inflammatory bowel disease. Inflammatory Bowel Diseases. ISSN 1078-0998. 15(1), p. 9–16. doi: 10.1002/ibd.20542. Full text in Research Archive
• Brackmann, Stephan; Andersen, Solveig Norheim; Aamodt, Geir; Frøydis, Langmark; Clausen, Ole Petter Fraas & Aadland, Erling [Show all 9 contributors for this article] (2009). Relationship between clinical parameters and the colitis-colorectal cancer interval in a cohort of patients with colorectal cancer in inflammatory bowel disease. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 44(1), p. 46–55. doi: 10.1080/00365520801977568. Full text in Research Archive
• Aamodt, Rolf; Jonsdottir, Kristin; Andersen, Solveig Norheim; Bondi, Johan Fridtjof; Bukholm, Geir & Bukholm, Ida Rashida Khan (2009). Differences in Protein Expression and Gene Amplification of Cyclins between Colon and Rectal Adenocarcinomas. Gastroenterology Research and Practice. ISSN 1687-6121. doi: 10.1155/2009/285830. Full text in Research Archive
• Færden, Arne Engebreyh; Sjo, Ole Helmer; Andersen, Solveig Norheim; Hauglann, Beate; Naimy, Nazir & Gravedaug, B [Show all 10 contributors for this article] (2008). Sentinel Node Mapping does not Improve Staging of Lymph Node Metastasis in Colonic Cancer. Diseases of the Colon & Rectum. ISSN 0012-3706. 51(6), p. 891–896. doi: 10.1007/s10350-007-9185-0. Full text in Research Archive
• Aamodt, Rolf; Bondi, Johan; Andersen, Solveig Norheim; Bukholm, Geir & Bukholm, Ida Rashida Khan (2008). Expression of Nuclear Beta-Catenin in Rectal Versus Colonic Cancers. Open Clinical Cancer Journal. 2, p. 13–17. doi: 10.2174/1874189400802010013. Full text in Research Archive
• Burum-Auensen, E; DeAngelis, PM; Schjølberg, Aasa Rambæk; Røislien, Jo; Andersen, Solveig Norheim & Clausen, Ole Petter Fraas (2007). Spindle proteins Aurora A and BUB1B, but not Mad2, are aberrantly expressed in dysplastic mucosa of patients with longstanding ulcerative colitis. Journal of Clinical Pathology. ISSN 0021-9746. 60, p. 1403–1408. doi: 10.1136/jcp.2006.044305. Full text in Research Archive
• Løvig, Tone; Andersen, Solveig Norheim; Clausen, Ole Petter Fraas & Rognum, Torleiv Ole (2007). Microsatellite instability in long-standing ulcerative colitis. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 42. doi: 10.1080/00365520601013747. Full text in Research Archive
• Guleng, Guttorm; Meling, Gunn Iren; Andersen, Solveig Norheim & Rognum, Torleiv Ole (2005). Mitochondrial microsatellite instability in colorectal carcinomas - frequency and association with nuclear microsatellite instability. Cancer Letters. ISSN 0304-3835. 219. Full text in Research Archive
• Faerden, Arne E.; Naimy, Nazir; Wiik, Pål; Reiertsen, Ola; Weyessa, Seyoum & Trønnes, Sigurd [Show all 8 contributors for this article] (2005). Total Mesorectal Excision for Rectal Cancer: Difference in Outcome for Low and High Rectal Cancer. Diseases of the Colon & Rectum. ISSN 0012-3706. 48(12), p. 2224–2231. Full text in Research Archive
• Andersen, Solveig Norheim; Halvorsen, Trine Grønhaug; Pedersen-Bjergaard, Stig; Rasmussen, Knut Einar; Tanum, Lars & Refsum, Helge (2003). Stereospecific determination of citalopram and desmethylcitalopram by capillary electrophoresis and liquid-phase microextraction. Journal of Pharmaceutical and Biomedical Analysis. ISSN 0731-7085. 33, p. 263–273. Full text in Research Archive
• Bukholm, Ida; Bondi, Johan Fridtjof; Wiik, Pål; Nesland, Jahn M; Andersen, Solveig Norheim & Bakka, Arne [Show all 7 contributors for this article] (2003). Presence of isolated tumour cells in mesenteric lymph nodes predicts poor prognosis in patients with stage II colon cancer. European Journal of Surgical Oncology. ISSN 0748-7983. 29(10), p. 862–866. Full text in Research Archive
• Andersen, Solveig Norheim; Halvorsen, Trine Grønhaug; Pedersen-Bjergaard, Stig & Rasmussen, Knut Einar (2002). Liquid-phase microextraction combined with capillary electrophoresis, a promising tool for the determination of chiral drugs in biological matrices. Journal of Chromatography A. ISSN 0021-9673. 963, p. 303–312. Full text in Research Archive Show summary

  A disposable device for liquid-phase microextraction (LPME) based on porous polypropylene hollow fibres has recently been introduced. In the present paper, LPME was combined with capillary electrophoresis (CE)and the combination was for the first time evaluated for chiral determination of drugs in biological matrices. The chiral antidepressant drug mianserin was selected as model compound. The mianserin enantiomers were extracted from 0.5 ml of plasma added internal standard and made alkaline with 0.25 ml of 2 M NaOH. The unionised analytes were extracted into di-n-hexyl ether impregnated in the pores of the hollow fibre, and into an acidic solution inside the hollow fibre. This resulted in a three-phase system where the extracts were aqueous, and hence directly compatible with the CE system. Efficient sample clean-up was seen and the extraction recovery was 80% for both enantiomers. Discrimination between the enantiomers in the extraction system was not observed. The limit of quantitation (S/N=10; 12.5 ng/ml for both enantiomers) and the limit of detection (S/N=3; 4 ng/ml for both enantiomers) were below the therapeutic range for mianserin. The method was validated and successfully applied to determine R- and S-mianserin in plasma samples from seven patients treated with mianserin, indicating that LPME¿CE is a promising combination for analysis of racemic drugs present in low concentrations in biological matrices.

• Løvig, Tone; Andersen, Solveig Norheim; Thorstensen, L.; Diep, Chieu; Meling, Gunn Iren & Lothe, Ragnhild A [Show all 7 contributors for this article] (2002). Strong HLA-DR expression in microsatellite stable carcinomas of the large bowel is associated with good prognosis. British Journal of Cancer. ISSN 0007-0920. 87, p. 756–762. Full text in Research Archive
• Løvig, Tone; Meling, Gunn Iren; Diep, Chieu; Thorstensen, L.; Andersen, Solveig Norheim & Lothe, Ragnhild A [Show all 7 contributors for this article] (2002). APC and CTNNB1 mutations in a large series of sporadic colorectal carcinomas stratified by MSI. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 37, p. 1184–1193. Full text in Research Archive
• Clausen, Ole Petter Fraas; Andersen, Solveig Norheim; Strømkjær, H.; Nielsen, V.; Rognum, Torleiv Ole & Bolund, L. [Show all 7 contributors for this article] (2001). A strategy combining Flow Sorting and and Comparative Genomic Hybridization for studying genetic aberrations at different stages of colorectal tumorigenesis in ulcerative colitis. Cytometry. ISSN 0196-4763. 43, p. 46–54. Full text in Research Archive
• Andersen, Solveig Norheim; Løvig, Tone; Clausen, Ole Petter Fraas; Bakka, Arne & Rognum, Torleiv Ole (1999). Villous, hypermucinous mucosa in long standing ulcerative colitis shows high frequency of K-ras mutations. Gut. ISSN 0017-5749. 45, p. 686–692. Full text in Research Archive
• Andersen, Solveig Norheim; Løvig, Tone; Clausen, Ole Petter Fraas; Bakka, Arne & Rognum, Torleiv Ole (1999). Villous, hypermucinous mucosa in log standing ulcreative colitis shows high frequency of K-ras mutations. Gut. ISSN 0017-5749. 45, p. 686–692. Full text in Research Archive
• Andersen, Solveig Norheim; Løvig, Tone; Fausa, Olav & Rognum, Torleiv Ole (1999). Germline and somatic mutations in exon 15 of the APS gene and K-ras mutations adenomas in patients with familial adenomatous polyposis (FAP). Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 34, p. 611–617. Full text in Research Archive
• Andreyev, H.J.N.; Andersen, Solveig Norheim; Brevik, Jarle; Gaudernack, Gustav; Clausen, Ole Petter Fraas & Angelis, Paula de [Show all 8 contributors for this article] (1998). Kirsten ras mutations in 2,721 patients with colorectal cancer: the «RASCA. Journal of the National Cancer Institute. ISSN 0027-8874. 90, p. 675–684. Full text in Research Archive
• Andersen, Solveig Norheim; Rognum, Torleiv Ole; Bakka, Arne & Clausen, Ole Petter Fraas (1998). Are elevated cerebrospinal fluid levels of IL-6 in sudden unexplained deaths, infectious deaths and deaths due to heart/lung disease in infants and children due to hypoxia? Acta Pædiatr 1998; 87: 819-824. Molecular Pathology. ISSN 1366-8714. 51, p. 327–332. Full text in Research Archive
• Hofstad, Bjørn; Vatn, Morten H; Andersen, Solveig Norheim; Owen, R.W.; Larsen, S. Melsen & Osnes, Magne (1998). The relationship between faecal bile acid profile with or without supplementation with calcium and antioxidants on recurrence and growth of colorectal polyps. European Journal of Cancer Prevention. ISSN 0959-8278. 7, p. 287–294. Full text in Research Archive
• Hofstad, Bjørn; Almendingen, Kari; Vatn, Morten H; Andersen, Solveig Norheim; Owen, R.B. & Larsen, S. Melsen [Show all 7 contributors for this article] (1998). Growth and recurrence of colorectal polyps: a double blind 3 years intervention with calcium and antioxidants. Digestion. ISSN 0012-2823. 59, p. 148–156. Full text in Research Archive
• Andersen, Solveig Norheim; Rognum, Torleiv Ole; Bakka, Arne & Clausen, Ole Petter Fraas (1998). Ki-67 ­ a useful marker in evaluation of dysplasia in ulcerative colitis. Molecular Pathology. ISSN 1366-8714. 51, p. 327–332. Full text in Research Archive
• Andersen, Solveig Norheim; Løvig, Tone; Breivik, Jarle; Lund, Eiliv; Gaudernack, Gustav & Meling, Gunn Iren [Show all 7 contributors for this article] (1997). K-ras mutations and prognosis in large bowel carcinomas. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 32, p. 62–69. Full text in Research Archive
• Andersen, Solveig Norheim; Breivik, Jarle; Løvig, Tone; Meling, Gunn Iren; Gaudernack, Gustav & Clausen, Ole Petter Fraas [Show all 11 contributors for this article] (1996). K-ras mutations and HLA-DR expression in large bowel adenomas. British Journal of Cancer. ISSN 0007-0920. 74, p. 99–108. Full text in Research Archive
• Hofstad, Bjørn; Vatn, Morten H & Andersen, Solveig Norheim (1996). Growth of colorectal polyps: Recovery and evaluation of unresected polyps for a period of 3 years. Gut. ISSN 0017-5749. 39, p. 449–456. Full text in Research Archive
• Andersen, Solveig Norheim & Hegna, Ida Kristin (1975). An in vitro study of the bactericidal effects on Escherichia coli of some bisbiguanides in aqueous solutions with various pH values. Meddelelser fra Norsk Farmaceutisk Selskap. ISSN 0029-1927. 37, p. 283–288. Full text in Research Archive

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• Alsøe, Lene; Wennerström, Anna Berit; Liu, Yan; Esbensen, Qin Ying; Bjørset, Randi & Penz, Christine [Show all 10 contributors for this article] (2018). Do APOBEC proteins contribute to genomic instability in colitis-associated colorectal cancer? Full text in Research Archive
• Alsøe, Lene; Wennerstrøm, Anna; Liu, Yan; Esbensen, Qin Ying; Bjørseth, Randi & Penz, Christine [Show all 10 contributors for this article] (2017). Do APOBEC proteins contribute to genomic instability in colitis-associated colorectal cancer? Full text in Research Archive
• Alsøe, Lene; Wennerstrøm, Anna; Liu, Yan; Esbensen, Qin Ying; Bjørseth, Randi & Penz, Christine [Show all 10 contributors for this article] (2017). Do APOBEC proteins contribute to genomic instability in colitis-associated colorectal cancer? Full text in Research Archive
• Brackmann, Stephan; Pretorius, Maria E.; Klepp, Pasquale Catherine; Clausen, Ole Petter Fraas; Andersen, Solveig Norheim & Vatn, Morten H [Show all 9 contributors for this article] (2013). The distribution of chromosomal and microsatellite instability in colorectal cancers related to inflammatory bowel disease. Journal of Clinical Oncology. ISSN 0732-183X. 31(15). Full text in Research Archive
• Brackmann, Stephan; Pretorius, Maria E.; Andersen, Solveig Norheim; Langmark, Frøydis; Clausen, Ole Petter Fraas & Vatn, Morten [Show all 7 contributors for this article] (2011). Large scale genomic instability in patients with colorectal cancer in inflammatory bowel disease. Association with clinicohistological factors and survival. Full text in Research Archive
• Aamodt, Rolf; Jonsdottir, Kristin; Bondi, Johan; Andersen, Solveig Norheim; Bukholm, Geir & Bukholm, Ida Rashida Khan (2008). SAMMENHENG MELLOM NIVÅ AV CYCLIN A I PRIMÆRTUMOR AV CANCER RECTI OG SENERE FOREKOMST AV LOKALT RESIDIV. Full text in Research Archive
• Aamodt, Rolf; Jonsdottir, Kristin; Andersen, Solveig Norheim; Bondi, Johan; Bukholm, Geir & Bukholm, Ida Rashida Khan (2008). Relation between level of cyclin A in primary tumors of rectal cancer and later appearance of local recurrence. Full text in Research Archive
• Brackmann, Stephan; Andersen, Solveig Norheim; Aamodt, Geir; Roald, Borghild Barth-H; Langmark, Frøydis & Clausen, Ole Petter Fraas [Show all 10 contributors for this article] (2008). Colorectal cancer in inflammatory bowel disease without distant dysplasia may be a specific entity. Full text in Research Archive
• Brackmann, Stephan; Andersen, Solveig Norheim; Aamodt, Geir; Roald, Borghild Barth-H; Langmark, Frøydis & Clausen, Ole Petter Fraas [Show all 10 contributors for this article] (2008). Colorectal cancer in inflammatory bowel disease without distant dysplasia may be a specific entity. Full text in Research Archive
• Brackmann, Stephan; Andersen, Solveig Norheim; Aamodt, Geir; Roald, Borghild Barth-H; Langmark, Frøydis & Clausen, Ole Petter Fraas [Show all 10 contributors for this article] (2008). Colorectal cancer in inflammatory bowel disease without distant dysplasia may be a specific entity. Gastroenterology. ISSN 0016-5085. 134(4), p. A292–A292. Full text in Research Archive
• Brackmann, Stephan; Andersen, Solveig Norheim; Aamodt, Geir; Roald, Borghild Barth-H; Langmark, Frøydis & Clausen, Ole Petter Fraas [Show all 10 contributors for this article] (2008). COLORECTAL CANCER IN INFLAMMATORY BOWEL DISEASE WITHOUT DISTANT DYSPLASIA MAY BE A SPECIFIC ENTITY. Full text in Research Archive
• Brackmann, Stephan; Andersen, Solveig Norheim; Aamodt, Geir; Roald, Borghild Barth-H; Langmark, Frøydis & Clausen, Ole Petter Fraas [Show all 10 contributors for this article] (2008). Widespread but not localized neoplasia in IBD worsens the prognosis of CRC. Full text in Research Archive
• Brackmann, Stephan; Andersen, Solveig Norheim; Aamodt, Geir; Langmark, Frøydis; Clausen, Ole Petter Fraas & Aadland, Erling [Show all 9 contributors for this article] (2007). Risk factors affecting duration of colitis-CRC interval in a cohort of CRC in IBD. Full text in Research Archive
• Brackmann, Stephan; Andersen, Solveig Norheim; Aamodt, Geir; Langmark, Frøydis; Clausen, Ole Petter Fraas & Aadland, Erling [Show all 9 contributors for this article] (2007). IBD relatert colorectalcancer overlevelelse i forhold til cancer screening. Full text in Research Archive
• Brackmann, Stephan; Andersen, Solveig Norheim; Aamodt, Geir; Langmark, Frøydis; Clausen, Ole Petter Fraas & Aadland, Erling [Show all 9 contributors for this article] (2006). RISKFACTORS AND SURVIVAL IN PATIENTS WITH IBD AND COLORECTAL CANCER. Full text in Research Archive
• Brackmann, Stephan; Andersen, Solveig Norheim; Aamodt, Geir; Fausa, Olav; Aadland, Erling & Rydning, Andreas [Show all 9 contributors for this article] (2006). Overlevelse ved Kronisk Inflammatorisk Tarmsydkom relatert Colorectal Cancer. Full text in Research Archive
• Andersen, Solveig Norheim; Halvorsen, Trine Grønhaug; Pedersen-Bjergaard, Stig; Rasmussen, Knut Einar; Tanum, Lars & Refsum, Helge (2002). STEREOSPECIFIC DRUG MONITORING OF ANTIDEPRESSANT DRUGS. Full text in Research Archive Show summary

  Many drugs used to treat psychiatric disorders contain one or more chiral centres. Most chiral drugs are available as the racemate, in which equal proportions of the two enantiomers are administered concurrently, although the two enantiomers may exhibit different pharmacodynamic and pharmacokinetic properties. Mianserin and citalopram are examples of chiral antidepressant drugs currently marketed as racemic mixtures, despite the fact that pharmacological activity reside primarily in one enantiomer. The S-enantiomer of both mianserin and citalopram are more active than the corresponding R-enantiomers. In the present project, stereospecific drug monitoring of mianserin and citalopram was accomplished by liquid-phase microextraction (LPME) combined with capillary electrophoresis (CE). Determinations of enantiomer concentrations of mianserin and citalopram were done in plasma from patients treated with racemic mianserin or citalopram. The results showed stereoselectivity in the metabolism of both mianserin and citalopram. A variation in the enantiomer ratio of both drugs was observed. No significant correlation between the administered dose and resulting plasma concentration could be demonstrated. The results suggest that separate determination of each enantiomer reflects antidepressant activity better than determination of the total mianserin or citalopram concentration.

• Andersen, Solveig Norheim; Halvorsen, Trine Grønhaug; Pedersen-Bjergaard, Stig & Rasmussen, Knut Einar (2002). Kiral terapikontroll vha. væskefasemikroekstraksjon og kapillærelektroforese. Enantiomer bestemmelse av mianserin i plasma hos psykiatriske pasienter. Full text in Research Archive Show summary

  Kirale legemidler blir i de fleste tilfeller gitt som racemater selv om de to enantiomere formene har forskjellig farmakologisk virkning, terapeutisk effekt og metabolisme. Optimalisering av hurtige kirale analyser med høy effektivitet og oppløsning er derfor viktig slik at kiral terapikontroll kan utføres og de ulike enantiomerenes farmakologiske egenskaper samt enantiomer renhet av kirale legemidler i farmasøytiske formuleringer kan studeres. Til nå har kromatografiske metoder vært mest utbredt i stereospesifikk legemiddel monitorering, men ved bruk av disse teknikkene er man avhengig av relativt dyre kirale stasjonærfaser. I løpet av de siste årene har kapillær elektroforese (CE) vist seg å være en teknikk som gir billige kirale analyser med høy effektivitet og oppløsning. Metoden gir i tillegg høy selektivitet og analysetidene er korte. CE er derfor et godt alternativ i kiral analyse. Ulempen er at man ikke har kunnet benytte CE til terapeutisk legemiddel monitorering da teknikken har for høye deteksjons- og kvantifiseringsgrenser. Væskefasemikroekstraksjon (LPME) er en relativt ny prøveopparbeidelsesteknikk som er spesielt godt egnet i kombinasjon med CE. Analytter blir ekstrahert fra en biologisk prøve gjennom en porøs hulfiber impregnert med organsikk løsningsmiddel og inn i en akseptorfase på innsiden av fiberen. Denne akseptorfasen er vandig i kombinasjon med CE, og ekstraktet kan dermed injiseres direkte i CE-apparatet. Det resulterende tre-fase systemet ved LPME gir spesielt god opprensing av prøvene. På grunn av en stor volumforskjell mellom prøveløsningen (0.5-4 ml) og akseptorfasen (25 µl) er det mulighet for høy oppkonsentrering av legemidlene. Denne høye oppkonsentreringen og den effektive prøveopprensingen sammen med fordelene av CE i kiral analyse gjør LPME/CE til en god kombinasjon ved kiral terapikontroll. I dette prosjektet ble det utviklet en metode hvor mianserinenantiomerene ble oppkonsentrert fra 0.5 ml plasma gjennom en hulfiber impregnert med heksyleter og inn i en akseptorfase bestående av 0.01 M HCl. Den enantiomere separasjonen ble utført ved bruk av hydroxypropyl-&#946;-cyclodekstrin som kiral selektor. Metoden ble validert og brukt til å bestemme R- og S-mianserin i plasmaprøver fra 7 pasienter behandlet med racemisk mianserin. Resultatene viste ulik hastighet av metabolismen til enantiomerene. Alle pasientene hadde høyest konsentrasjon av den mest aktive enantimeren, S-mianserin. I tillegg kunne man se at konsentrasjonen av S-mianserins hovedmetabolitt var tilsvarende lavere i forhold til konsentrasjonen av R-mianserins hovedmetabolitt.

• Halvorsen, Trine Grønhaug; Andersen, Solveig Norheim; Rasmussen, Knut Einar & Pedersen-Bjergaard, Stig (2002). Chiral analysis of drugs at the low ng/ml level in human plasma by liquid-phase microextraction and capillary electrophoresis. Full text in Research Archive Show summary

  In the present work, the potential of liquid-phase microextraction (LPME) combined with capillary zone electrophoresis(CZE) for the chiral monitoring of drugs in human plasma was evaluated. Mianserin and citalopram were selected as model drugs which are administered as racemates, and the concentration leves studied where within the range from 10 to 1000 ng/ml (which included the therapeutic levels). By LPME, the drugs were extracted from 0.5 ml of plasma through an organic liquid (typically di-hexyl ether) immobilised in the pores of a small porous polypropylene hollow fibre and into a small acceptor solution of 25 µl 10 mM HCl inside the lumen of the hollow fibre. Subsequently, the acceptor phase was directly subjected to analysis by CZE utilising different charged cyclodextrins as chiral selectors. With LPME, the drugs were preconcentrated by a factor 15 to 20 which enabled their detection down to the 5-10 ng/ml level by CZE with UV-detection. In addition, the three-phase nature of LPME ensured very high clean-up from plasma eliminating most potential interferences. In conclusion, the high analyte enrichment of LPME was successfully combined with the excellent chiral resolving power of CZE and enabled rapid determinations of drugs in human plasma an the low ng/ml level.

• Andersen, Solveig Norheim; Halvorsen, Trine Grønhaug; Pedersen-Bjergaard, Stig; Rasmussen, Knut Einar; Tanum, Lars & Refsum, Helge (2002). CHIRAL ANALYSIS OF MIANSERIN IN PLASMA BY LIQUID-PHASE MICROEXTRACTION AND CAPILLARY ELECTROPHORESIS. Full text in Research Archive Show summary

  Chiral drugs are usually administered as racemates although the two enantiomers often exhibit different behaviour in terms of pharmacological action and therapeutic efficiency. The optimisation of fast enantioselective analytical methods offering high efficiency and resolution is, therefore, important for the study of pharmacokinetic and pharmacodynamic properties of racemic drugs, and to control the enantiomeric purity of pharmaceutical preparations. In the present work a relatively new sample preparation technique called liquid-phase microextraction was combined with capillary electrophoresis, and the combination was evaluated for chiral determination of drugs in biological matrices. The antidepressant drug mianserin was chosen as a model compound. Mianserin is a chiral drug administered as a racemic mixture. The two enantiomers of mianserin exhibit different degree of antidepressant activity, the S-enantiomer being significantly more active than the R-enantiomer. The mianserin enantiomers were extracted from 0.5 ml of plasma samples made alkaline with NaOH, through a thin phase of hexyl ether inside the pores of a polypropylene hollow fibre, and finally into a 25 µl acidic solution inside the hollow fibre. Following sample clean-up and preconcentration by liquid-phase microextraction, the acceptor solutions were analyzed by capillary electrophoresis. The enantiomeric separation was performed using a cyclodextrin as the chiral selector. The method was validated and successfully applied to determine R- and S-mianserin in plasma samples from seven patients treated with mianserin. The results indicate that liquid-phase microextraction combined with capillary electrophoresis is a promising tool for analysis of racemic drugs present in low concentrations in biological matrices.

• Andersen, Solveig Norheim; Halvorsen, Trine Grønhaug; Pedersen-Bjergaard, Stig & Rasmussen, Knut Einar (2001). Kiral analyse av mianserin i plasma hos psykiatriske pasienter Bestemmelse ved hjelp av væskefasemikroekstraksjon og kapillærelektroforese. Full text in Research Archive Show summary

  Kirale legemidler blir i de fleste tilfeller gitt som racemater selv om de to enantiomere formene er forskjellig med henblikk på farmakologisk virkning, terapeutisk effekt og metabolisme. Optimalisering av hurtige kirale analyser som har høy effektivitet og oppløsning er derfor viktig slik at farmakodynamiske og farmakokinetiske egenskaper av racemiske legemidler samt renhet av enantiomerene i farmasøytiske formuleringer kan studeres. Til nå har kromatografiske metoder vært mest utbredt i stereospesifikk legemiddel monitorering, men ved bruk av disse teknikkene er man avhengig av relativt dyre kirale stasjonærfaser. I løpet av de siste årene har kapillær elektroforese (CE) vist seg å være en teknikk som gir billige kirale analyser med høy effektivitet og oppløsning. I tillegg gir metoden høy selektivitet og analysetidene er korte. CE er derfor et godt alternativ i kiral analyse. Ulempen er at man ikke har kunnet benytte CE til terapeutisk legemiddel monitorering da teknikken har for høye deteksjons- og kvantifiseringsgrenser. Væskefasemikroekstraksjon (LPME) er en relativt ny prøveopparbeidelsesteknikk som er spesielt godt egnet i kombinasjon med CE. Analytter blir ekstrahert fra en biologisk prøve gjennom en porøs hulfiber og inn i en akseptorfase på innsiden av fiberen. Denne akseptorfasen er vandig i kombinasjon med CE, noe som resulterer i et tre-fase system som gir spesielt god opprensing av prøvene. På grunn av en stor volumforskjell mellom prøveløsningen (0.5-4 ml) og akseptorfasen (25 µl) er det mulighet for høy oppkonsentrering av legemidlene. Denne høye oppkonsentreringen og den effektive prøveopprensingen sammen med fordelene av CE i kiral analyse gjør LPME/CE til en god kombinasjon i enantiomere seperasjoner. I dette prosjektet har vi utviklet en metode hvor mianserinenantiomerene ble oppkonsentrert fra 0.5 ml plasma gjennom en hulfiber impregnert med heksyleter og inn i en akseptorfase bestående av 0.01 M HCl. Den enantiomere separasjonen ble utført ved å bruke hydroxypropyl-&#946;-cyclodekstrin som kiral selektor. Metoden ble validert og brukt til å bestemme R- og S-mianserin i plasmaprøver fra 7 pasienter behandlet med racemisk mianserin. Resultatene viste ulik hastighet av metabolismen til enantiomerene. Alle pasientene hadde høyest konsentrasjon av den mest aktive enantimeren, S-mianserin. I tillegg kunne man se at konsentrasjonen av S-mianserins hovedmetabolitt var tilsvarende lavere i forhold til konsentrasjonen av R-mianserins hovedmetabolitt. Resultatene av analysene vil bli diskutert.

• Andersen, Solveig Norheim; Halvorsen, Trine Grønhaug; Pedersen-Bjergaard, Stig & Rasmussen, Knut Einar (2001). Liquid-phase microextraction combined with capillary electrophoresis for the determination of mianserin enantiomers in plasma. Full text in Research Archive Show summary

  The combination of liquid-phase microextraction (LPME), a recently developed sample preparation technique [1], with capillary electrophoresis (CE), resulted in a powerful method for the determination of mianserin enantiomers in plasma. CE provides chiral analysis with high efficiency, resolution and selectivity at a low cost. However, relatively high detection limits have restricted the use of chiral CE in therapeutic drug monitoring where only small amounts of sample are available. LPME is a sample preparation technique especially suitable for combination with CE. In LPME analytes are extracted from biological matrices through a porous polypropylene hollow fibre impregnated with an organic solvent and into an acceptor phase, which is aqueous in combination with CE. This three-phase system results in efficient sample clean-up. A large volume difference between the sample solution (0.5-4 ml) and the acceptor solution (25 µl) results in high preconcentration. High preconcentration and efficient sample clean-up together with the advantages of CE in chiral analysis makes LPME/CE an ideal combination for enantiomeric separations. In this project, mianserin enantiomers were extracted from 0.5 ml of plasma samples, through a hollow fibre impregnated with hexyl ether and into an acceptor phase consisting of 0.01 M HCl. The enantiomeric separation was performed using hydroxypropyl-&#946;-cyclodextrin as the chiral selector. The method was validated and used for determination of R- and S-mianserin in plasma samples from 7 patients treated with mianserin. [1] K.E.Rasmussen, S.Pedersen-Bjergaard, M.Krogh, H.G.Ugland and T.Grønhaug, J. Chromatogr. A, 873 (2000) 3.

• Hofstad, Bjørn; Vatn, Morten H; Andersen, Solveig Norheim; Owen, R.B.; Larsen, S. Melsen & Osnes, Magne (1997). Colorectal cancer and bile acid. Full text in Research Archive
• Andersen, Solveig Norheim (1999). Prognostic significance of classical versus immunological and molecular cancer markers. A study of the large bowel. Universitetet i Oslo. Full text in Research Archive
• Andersen, Solveig Norheim (1999). Prognostic significance of classical versus immunological and molecular cancer marker. A study of large bowel. Full text in Research Archive

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