| 1. |
- Emterling, A, et al.
(författare)
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Clinicopathological significance of microsatellite instability and mutated RIZ in colorectal cancer
- 2004
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 15:2, s. 242-246
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several studies have shown that microsatellite instability (MSI) is related to favourable survival in colorectal cancer patients but there are controversial results. Tumour suppressor gene RIZ is a susceptible mutational target of MSI. However, its clinicopathological significance has not been investigated. We investigated the prognostic significance of MSI in Swedish colorectal cancer patients and the clinicopathological significance of RIZ mutations. Patients and methods: We analysed 438 colorectal adenocarcinomas for MSI by microsatellite analysis. Among them, 29 MSI and 28 microsatellite stable (MSS) tumours were examined for RIZ mutations by DNA sequencing. Results: MSI (13% of 438 cases) was not associated with survival (rate ratio=0.97, 95% confidence interval =0.57-1.64, P=0.90), although it was related to proximal tumour (P <0.001), poor differentiation and mucinous carcinomas (P <0.001), multiple tumours (P=0.01) and negative/weak expression of hMLH1 (P=0.03). RIZ mutations were detected in 31% of 29 MSI tumours but in none of the 28 MSS tumours. The mutations were related to female (P=0.01), proximal tumour (P=0.01), stage B (P=0.01) and poor differentiation (P=0.047). Conclusions: MSI was not a prognostic factor in the Swedish patients included in this study. Clinicopathological variables associated with RIZ mutations might be a consequence of the MSI characteristics.
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| 2. |
- Evertsson, Sofia, 1972-, et al.
(författare)
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Microsatellite instability and MBD4 mutation in unselected colorectal cancer
- 2003
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 23:4, s. 3569-3574
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We investigated the prognostic significance of microsatellite instability (MSI) and the association with clinicopathological factors in colorectal cancer, and further identified MBD4 mutations and their clinicopathological significance.PATIENTS AND METHODS: MSI was analyzed in 201 colorectal cancers. Sequencing analysis of MBD4 was performed in 26 MSI and 28 microsatellite stable (MSS) tumors.RESULTS: Twenty-seven tumors (13.4%) were MSI but did not correlate with improved survival. MSI was significantly correlated with proximal colon tumors (p < 0.001), poor differentiation or mucinous type (p = 0.005) and multiple tumors (p = 0.04). MBD4 mutations were found in 15% MSI but not in MSS tumors. The mutated cases showed female overrepresentation, proximal site and poorly-differentiated/mucinous type.CONCLUSION: MSI was not correlated with survival, but shared other features associated with MSI in colorectal cancer as demonstrated by others. The clinicopathological variables associated with the MBD4 mutations were probably the reflection of MSI features.
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| 3. |
- Moparhti, Satish Babu, et al.
(författare)
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Expression of MAC30 protein is related to survival and biological variables in primary and metastatic colorectal cancers
- 2007
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Ingår i: International Journal of Oncology. - 1019-6439 .- 1791-2423. ; 30:1, s. 91-95
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Tidskriftsartikel (refereegranskat)abstract
- MAC30 is highly expressed in several types of tumors including colorectal cancers, however, its clinicopathological and biological significance in colorectal cancers is currently not known. The aim of our study was to investigate MAC30 expression in distant normal mucosa, adjacent normal mucosa, primary tumors and metastases of colorectal cancer, and to determine the relationship between MAC30 expression and clinicopathological and biological variables. MAC30 expression was immunohistochemically examined in distant normal mucosa (n = 54), adjacent normal mucosa (n = 123), primary tumors (n = 217) and lymph node metastases (n = 56) from colorectal cancer patients. MAC30 cytoplasmic expression was increased from distant normal mucosa to primary tumor and to metastasis (p < 0.0001-0.04). Furthermore, 40% primary and 37% metastatic tumors showed stronger cytoplasmic expression of MAC30 at the tumor invasive margins compared to inner tumor areas. Strong cytoplasmic expression of MAC30 in the metastasis was related to a poor prognosis (p = 0.04). MAC30 cytoplasmic expression was positively related to expression of proliferating cell nuclear antigen (p = 0.04), p53 (p = 0.04), nucleoporin 88 (p = 0.001), legumain (p = 0.004) and particularly interesting new cysteine-histidine rich protein (p = 0.004). However, MAC30 expression in the nucleus and stroma did not have any clinicopathological and biological significance (p > 0.05). In conclusion, MAC30 protein may play a role in development of colorectal cancer, and can be considered as a prognostic factor.
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| 4. |
- Pfeifer, Daniella, et al.
(författare)
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Protein expression following gamma-irradiation relevant to growth arrest and apoptosis in colon cancer cells with mutant p53
- 2009
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Ingår i: Journal of Cancer Research and Clinical Oncology. - : Springer Science and Business Media LLC. - 0171-5216 .- 1432-1335. ; 135:11, s. 1583-1592
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Tidskriftsartikel (refereegranskat)abstract
- We previously found that p53, p73, survivin and PRL were implicated in the outcome of radiotherapy in rectal cancer patients. In the present study, we tried to understand mechanisms of colon cancer cell line response to radiation based on protein expression related to proliferation and apoptosis. KM12C, KM12SM and KM12L4a, cell lines with one origin, were radiated with 0, 10 or 15 Gy γ-radiation. Radiosensitivity was determined with cell cycle and apoptosis analysis, and protein expression of TAp73, ΔNp73, mutated p53, survivin and PRL-3 was determined by Western blot. KM12C showed transient G2-arrest, low apoptosis and up-regulation of resistance factors such as PRL-3. In KM12C expression of ΔNp73 increased after 10Gy, but not after 15Gy. KM12SM had permanent G2-arrest, low apoptosis and showed up-regulation of the anti-apoptotic survivin and down-regulation of the pro-apoptotic TAp73 and the radioresistance factor PRL-3 was down-regulated. KM12L4a, the most radiosensitive cell line, showed up-regulation of TAp73 and down-regulation/no up-regulation of resistance factors such as ΔNp73, survivin and PRL-3 after radiation. In conclusion, the KM12C cell line was more radioresistant than KM12L4a regarding apoptosis and certain apoptotic proteins. The radiosensitivity of KM12L4a might partly depend on the lack of up-regulation of proteins negative for the outcome of radiotherapy.
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| 5. |
- Sun, Xiao-Feng, 1959-, et al.
(författare)
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Polymorphisms in sulfotransferase 1A1 and glutathione S-transferase P1 genes in relation to colorectal cancer risk and patients' survival
- 2005
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Ingår i: World Journal of Gastroenterology. - 1007-9327 .- 2219-2840. ; 11:43, s. 6875-6879
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To examine whether polymorphisms in SULT1A1 and GSTP1 genes contribute to colorectal cancer development and whether they are associated with clinicopathological variables are not well identified. Methods: We examined the genotypes of 125 colorectal cancer patients and 666 healthy controls in a Swedish population by using PCR restriction fragment length polymorphism (RFLP). Results: SULT1A1 *2/*2 genotype (OR = 2.49, 95%CI = 1.48-4.19, P = 0.0002) and *2 allele (OR = 1.56, 95%CI = 1.16-2.10, P = 0.002) had an effect on colorectal cancer susceptibility, while GSTP1 genotype was without effect. However, GSTP1 G-type predicted a worse prognosis in the patients independently of gender, age, Dukes' stage, growth pattern, and differentiation (P = 0.03). Conclusion: Polymorphism in SULT1A1 may predispose to colorectal cancer and GSTP1 may be a biological indicator of prognosis in the patients. © 2005 The WJG Press and Elsevier Inc. All rights reserved.
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| 6. |
- Wallin, Lisa, et al.
(författare)
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Capricious credibility - legal assessments of voluntariness in Swedish negligent rape judgements
- 2021
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Ingår i: Nordic Journal of Criminology. ; 22:1, s. 3-22
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Tidskriftsartikel (refereegranskat)abstract
- A new rape legislation, premised on the requirement of voluntariness, entered into force in Sweden during 2018. This article examines the application and interpretation of voluntariness in Swedish negligent rape judgements with a unique combination of the theoretical perspectives’ sociology of emotion and feminist-legal studies. The material consists of 12 court judgements, from the period 2018–2020, analysed by means of thematic content analysis. The findings show that the judgements in negligent rape cases are based on an evaluation of credibility, supported by evidence that consists of witness statements. These evaluations entail emotions and stereotypes about gender and sexuality, pertaining to rape myths – leading to inconsistent outcomes. Yet, some fundamental assumptions about gender and sexuality are challenged, indicating that the new law may invite discursive shifts and enhanced reflexivity in legal reasoning. The findings are valuable in the work to minimize legal discrimination and secure equality before the law.
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| 7. |
- Wallin, Martin, 1976, et al.
(författare)
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Sponsored spin-offs, industrial growth and change
- 2006
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Ingår i: Technovation. - Amsterdam : Elsevier. - 0166-4972 .- 1879-2383. ; 26:5-6, s. 611-620
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Tidskriftsartikel (refereegranskat)abstract
- This paper focuses on the role of sponsored spin-offs for industrial growth and dynamics. A sponsored spin-off is a firm born out of the venturing activities and the active involvement of an established organization; in this paper the latter in the form of retained partial ownership in the new firm. Sponsored spin-offs are one mechanism whereby the respective potential advantages of large and new firms may be exploited. Little is known about the nature and magnitude of contributions by existing firms to the creation of new technology-based firms and the effects these new firms have on innovation, change and renewal.In this paper, an empirical sample of 101 Swedish IPO firms is used in the analysis of three research questions. (1) Are sponsored spin-offs an important mechanism for the creation of new technology-based firms? (2) Are sponsored spin-off firms important for industrial growth? (3) Are sponsored spin-offs influencing industrial renewal and change? The results add to the understanding of how, and to what degree the venturing activities of existing firms contribute to the creation of new firms, as well as how and to what extent these spin-offs differ from other new firms in terms of their impact on industrial growth and change.
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| 8. |
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| 9. |
- Wallin, Åsa, 1976-, et al.
(författare)
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Anticancer effect of SN-38 on colon cancer cell lines with different metastatic potential
- 2008
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Ingår i: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 19:6, s. 1493-1498
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Tidskriftsartikel (refereegranskat)abstract
- SN-38 is an active metabolite of the topoisomerase I inhibitor irinotecan. The mechanism behind its antitumor effect in colorectal cancer is not fully understood. In this study, we examined the response of colon cancer cell lines with different metastatic potential to SN-38. The parental human colon cancer cell line KM12C and its two highly metastatic derivatives KM12SM and KM12L4a were cultivated in 5% CO2 at 37°C for 24 h and then exposed to SN-38 (2.5 µg/ml) at 37°C for 4, 24 and 48 h, respectively. The cell cycle was measured by flow cytometry, apoptotic activity was determined by flow cytometry and immunocytochemistry and the expression of topoisomerase I, Bax and survivin proteins were examined by Western blot. The exposure of the cells to SN-38 induced S-phase and G2 arrest (P<0.0001) and the KM12L4a cells had the highest response in a time-dependent manner (P<0.0001). The rates of apoptosis in the KM12SM (P=0.001) and KM12L4a cell lines (P=0.01) were increased time-dependently, though there was no such change in the KM12C cells. The expression of topoisomerase I protein was decreased in each cell line tested and the expression of Bax protein was increased, especially in KM12L4a. In conclusion, the effect of SN-38 on the colon cancer cell lines was mediated via conducting S-phase and G2 arrest and apoptosis. This effect was found in the cell lines with higher metastatic potentials, indicating that SN-38 can be used to treat advanced colon cancers.
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| 10. |
- Wallin, Åsa, 1976-, et al.
(författare)
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Gene Expression Profile of Colon Cancer Cell Lines Treated with SN-38
- 2010
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Ingår i: Chemotherapy. - : S. Karger AG. - 0009-3157 .- 1421-9794. ; 56:1, s. 17-25
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Colorectal cancer is the third most common form of cancer in the industrial countries. Due to advances regarding the treatments, primarily development of improved surgical methods and the ability to make the earlier diagnosis, the mortality has remained constant during the past decades even though the incidence in fact has increased. To improve chemotherapy and enable personalised treatment, the need of biomarkers is of great significance. In this study, we evaluated the gene expression profiles of the colon cancer cell lines treated with SN-38, the active metabolite of topoisomerase-1 inhibitor irinotecan which leads to cell cycle arrest and apoptosis. Material and Methods: The study included 3 colon cancer cell lines: KM12C, KM12SM and KM12l4a. The 3 cell lines were treated with SN-38, and samples were obtained after 24 and 48 hour treatments. The gene expression analyses were performed using oligonucleotide microarrays comprising of similar to 27,000 spots where the untreated controls were compared to the SN-38-treated samples. Results: Unsupervised clustering clearly distinguished the treated cell lines from the untreated. Supervised analysis identified 3,974 significant genes (p = 0.05) differentiating the treated samples from the untreated, majority of which were down-regulated after treatment. The top-ranked down-regulated genes in the treated cell lines included those related to receptor and kinase activity, signal transduction, apoptosis, RNA processing, protein metabolism and transport, cell cycle and transcription. A smaller number of genes were up-regulated in the cell lines after treatment and included genes involved in apoptosis, transcription, development and differentiation. Conclusions: These results demonstrate that the expression of the genes involved in cell proliferation and apoptosis as well as RNA, DNA and protein metabolism were affected by SN-38. The impact of certain genes on colorectal cancer development needs to be further evaluated; however, these results could serve as a basis for further studies in order to find targets for irinotecan treatment. Copyright (C) 2010 S. Karger AG, Basel
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