| 1. |
- 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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| 2. |
- Alexandersson, Nathalie, et al.
(författare)
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Determinants of variable resource use for multidisciplinary team meetings in cancer care
- 2018
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Ingår i: Acta Oncologica. - 0284-186X. ; 57:5, s. 675-680
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multidisciplinary team meetings (MDTMs) have developed into standard of care to provide expert opinion and to grant evidence-based recommendations on diagnostics and treatment of cancer. Though MDTMs are associated with a range of benefits, a growing number of cases, complex case discussion and an increasing number of participants raise questions on cost versus benefit. We aimed to determine cost of MDTMs and to define determinants hereof based on observations in Swedish cancer care. Methods: Data were collected through observations of 50 MDTMs and from questionnaire data from 206 health professionals that participated in these meetings. Results: The MDTMs lasted mean 0.88 h and managed mean 12.6 cases with mean 4.2 min per case. Participants were mean 8.2 physicians and 2.9 nurses/other health professionals. Besides the number of cases discussed, meeting duration was also influenced by cancer diagnosis, hospital type and use of video facilities. When preparatory work, participation and post-MDTM work were considered, physicians spent mean 4.1 h per meeting. The cost per case discussion was mean 212 (range 91–595) EUR and the cost per MDTM was mean 2675 (range 1439–4070) EUR. Conclusions: We identify considerable variability in resource use for MDTMs in cancer care and demonstrate that 84% of the total cost is derived from physician time. The variability demonstrated underscores the need for regular and structured evaluations to ensure cost effective MDTM services.
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| 3. |
- Arildsen, Nicolai Skovbjerg, et al.
(författare)
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Involvement of chromatin remodeling genes and the Rho GTPases RhoB and CDC42 in ovarian clear cell carcinoma
- 2017
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Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 7:MAY, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Ovarian clear cell carcinomas (OCCCs) constitute a rare ovarian cancer subtype with distinct clinical features, but may nonetheless be difficult to distinguish morphologically from other subtypes. There is limited knowledge of genetic events driving OCCC tumorigenesis beyond ARID1A, which is reportedly mutated in 30-50% of OCCCs. We aimed to further characterize OCCCs by combined global transcriptional profiling and targeted deep sequencing of a panel of well-established cancer genes. Increased knowledge of OCCC-specific genetic aberrations may help in guiding development of targeted treatments and ultimately improve patient outcome. Methods: Gene expression profiling of formalin-fixed, paraffin-embedded (FFPE) tissue from a cohort of the major ovarian cancer subtypes (cohort 1; n = 67) was performed using whole-genome cDNA-mediated Annealing, Selection, extension and Ligation (WG-DASL) bead arrays, followed by pathway, gene module score, and gene ontology analyses, respectively. A second FFPE cohort of 10 primary OCCCs was analyzed by targeted DNA sequencing of a panel of 60 cancer-related genes (cohort 2). Non-synonymous and non-sense variants affecting single-nucleotide variations and insertions or deletions were further analyzed. A tissue microarray of 43 OCCCs (cohort 3) was used for validation by immunohistochemistry and chromogenic in situ hybridization. Results: Gene expression analyses revealed a distinct OCCC profile compared to other histological subtypes, with, e.g., ERBB2, TFAP2A, and genes related to cytoskeletal actin regulation being overexpressed in OCCC. ERBB2 was, however, not overexpressed on the protein level and ERBB2 amplification was rare in the validation cohort. Targeted deep sequencing revealed non-synonymous variants or insertions/deletions in 11/60 cancer-related genes. Genes involved in chromatin remodeling, including ARID1A, SPOP, and KMT2D were frequently mutated across OCCC tumors. Conclusion: OCCCs appear genetically heterogeneous, but harbor frequent alterations in chromatin remodeling genes. Overexpression of TFAP2A and ERBB2 was observed on the mRNA level in relation to other ovarian cancer subtypes. However, overexpression of ERBB2 was not reflected by HER2 amplification or protein overexpression in the OCCC validation cohort. In addition, Rho GTPase-dependent actin organization may also play a role in OCCC pathogenesis and warrants further investigation. The distinct biological features of OCCC discovered here may provide a basis for novel targeted treatment strategies.
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| 4. |
- Bartuma, Katarina, et al.
(författare)
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Discrepancies between estimated and perceived risk of cancer among individuals with hereditary nonpolyposis colorectal cancer
- 2007
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Ingår i: Genetic Testing. - : Mary Ann Liebert Inc. - 1557-7473 .- 1090-6576. ; 11:2, s. 183-186
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Tidskriftsartikel (refereegranskat)abstract
- Communicating cancer risk and recommending adequate control programs is central for genetic counseling. Individuals affected by hereditary nonpolyposis colorectal cancer (HNPCC) are at about 80% life-time risk of colorectal cancer and for female carriers 40-60% risk of endometrial cancer and 10-15% risk of ovarian cancer. The perceived risk among mutation carriers may, however, deviate from the risk communicated and has been demonstrated to influence adherence to control programs. We investigated the perceived cancer risk among HNPCC mutation carriers (n = 47) and correlated the findings to individual characteristics. A perceived risk of colorectal cancer above 60% was reported by 22/45 individuals, and only one out of five mutation carriers reported a perceived risk > 80%. Female mutation carriers, individuals below age 50, and individuals who received their oncogenetic counseling within 1 year prior to the study reported higher, albeit not significantly, perceived risks of colorectal cancer. Higher perceived risks were also reported by individuals who had lost a parent to HNPCC-related cancer at early age, whereas individuals with a personal history of cancer did not report a higher perceived risk. Regarding gynecological cancer, 6/18 females reported a perceived risk of 40-60% for endometrial cancer, whereas the remaining women both underestimated and overestimated their risk, and none of the women referred to the risk of ovarian cancer. We conclude that despite educational efforts and an increasing amount of data on the cancer risk in HNPCC, a minority of the mutation carriers report a perceived risk at the same level as that communicated during oncogenetic counseling.
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| 5. |
- Bartuma, Katarina, et al.
(författare)
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Family perspectives in lynch syndrome becoming a family at risk, patterns of communication and influence on relations
- 2012
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Ingår i: Hereditary Cancer in Clinical Practice. - : Springer Science and Business Media LLC. - 1897-4287. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: A growing number of individuals are diagnosed with hereditary cancer. Though increased levels of anxiety and depression have been demonstrated around the time of genetic counselling, most individuals handle life at increased risk well. Data have, however, been collected on individual basis, which led us to focus on family perspectives of hereditary cancer. Methods: Lynch syndrome represents a major type of hereditary colorectal and gynaecological cancer. We preformed open-ended interviews with 27 informants from 9 Lynch syndrome families. Inductive content analysis revealed three major themes: transition to a risk family, patterns of communication and influence on family relations and individual roles. Results: Family members described how learning about Lynch syndrome shifted focus from daily issues to concerns about cancer. Changes in communication related to difficulties in talking to children about heredity and informing new family members and distant relatives about an increased risk of cancer. Influence on relations was exemplified by family members taking on different roles, e. g. females often being responsible for coordinating information about heredity and providing support. Families in which members had experienced cancer at young age typically informed children soon after learning about heredity and at young age, whereas families with experience of cancer at higher age postponed information and thereby also genetic counselling. Conclusions: Three major family perspectives are described in Lynch syndrome families; becoming a risk family, patterns of communication and influence on family relations. Since these issues are central, our findings suggests that such family perspectives should be considered during genetic counselling in order to contribute to information spread, help family members cope with the increased risk, and motivate family members at risk to undergo surveillance.
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| 6. |
- Bartuma, Katarina, et al.
(författare)
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Genetic profiles distinguish different types of hereditary ovarian cancer.
- 2010
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Ingår i: Oncology Reports. - : Spandidos Publications. - 1791-2431 .- 1021-335X. ; 24:4, s. 885-895
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Tidskriftsartikel (refereegranskat)abstract
- Heredity represents the strongest risk factor for ovarian cancer with disease predisposing mutations identified in 15% of the tumors. With the aim to identify genetic classifiers for hereditary ovarian cancer, we profiled hereditary ovarian cancers linked to the hereditary breast and ovarian cancer (HBOC) syndrome and the hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Genome-wide array comparative genomic hybridization was applied to 12 HBOC associated tumors with BRCA1 mutations and 8 HNPCC associated tumors with mismatch repair gene mutations with 24 sporadic ovarian cancers as a control group. Unsupervised cluster analysis identified two distinct subgroups related to genetic complexity. Sporadic and HBOC associated tumors had complex genetic profiles with an average 41% of the genome altered, whereas the mismatch repair defective tumors had stable genetic profiles, with an average 18% of the genome altered. Losses of 4q34, 13q12-q32 and 19p13 were overrepresented in the HBOC subset. Discriminating genes within these regions include BRCA2, FOXO1A and RB1. Gains on chromosomes 17 and 19 characterized the HNPCC tumors, but target genes herein are unknown. The results indicate that HBOC and HNPCC associated ovarian cancer develop along distinct genetic pathways and genetic profiles can thus be applied to distinguish between different types of hereditary ovarian cancer.
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| 7. |
- Bartuma, Katarina, et al.
(författare)
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Knowledge about hereditary nonpolyposis colorectal cancer; mutation carriers and physicians at equal levels
- 2009
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Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Identification and adequate management of individuals at risk for hereditary nonpolyposis colorectal cancer (HNPCC) is crucial since surveillance programmes reduce morbidity and mortality. We investigated knowledge about key features of HNPCC in at risk individuals and physicians in surgery, gynecology and oncology. Methods: Data were collected using a questionnaire which was answered by 67 mutation carriers and 102 physicians from the southern Swedish health care region. The statements were related to colorectal cancer, heredity and surveillance and the physicians were also asked questions about cancer risks and surveillance strategies. Results: Both groups answered questions on colorectal cancer risk, surveillance and genetic testing well, whereas answers about inheritance and risks for HNPCC associated cancer were less accurate. Only half of the family members and one third of the physicians correctly estimated the risk to inherit an HNPCC predisposing mutation. Among family members, young age (<57 years), female sex and recent genetic counseling significantly correlated with better results. Physicians generally underestimated the risk of HNPCC associated cancers and three out of four suggested a later starting age for surveillance than recommended. Conclusion: The finding of similar levels of knowledge about key features of HNPCC in at risk individuals and physicians reflect the challenge physicians face in keeping up to date on hereditary cancer and may have implications for the clinical management and professional relations with HNPCC family members.
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| 8. |
- Bartuma, Katarina, et al.
(författare)
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Ovarian cancer at young age: the contribution of mismatch-repair defects in a population-based series of epithelial ovarian cancer before age 40.
- 2007
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Ingår i: International Journal of Gynecological Cancer. - : BMJ. - 1048-891X .- 1525-1438. ; 17, s. 789-793
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Tidskriftsartikel (refereegranskat)abstract
- At least one of ten patients with ovarian cancer is estimated to develop their tumor because of heredity with the breast and ovarian cancer syndrome due to mutations in the BRCA1 and BRCA2 genes and hereditary nonpolyposis colorectal cancer (HNPCC) being the major genetic causes. Cancer at young age is a hallmark of heredity, and ovarian cancers associated with HNPCC have been demonstrated to develop at a particularly early age. We used the Swedish Cancer Registry to identify a population-based series of 98 invasive epithelial ovarian cancers that developed before 40 years. Mucinous and endometrioid cancers were overrepresented and were diagnosed in 27% and 16% of the tumors, respectively. Immunostaining using antibodies against MLH1, PMS2, MSH2, and MSH6 was used to assess the mismatch-repair status and revealed loss of expression of MLH1/PMS2 in two cases, loss of MSH2/MSH6 in one case, and loss of MSH6 only in three tumors. A microsatellite instability–high phenotype was verified in five of six tumors. Based on the identified mutations and family history of cancer, several of these individuals are likely to be affected by HNPCC. We conclude that although the causes of the vast majority of epithelial ovarian cancer at young age are unknown, HNPCC should be considered because of the high risk of metachronous colorectal cancer in the individual and the possibility of preventing additional cancers in the family through control programs.
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| 9. |
- Bartuma, Katarina, et al.
(författare)
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Response to letter of Escobar et al.
- 2008
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Ingår i: International Journal of Gynecological Cancer. - : BMJ. - 1048-891X .- 1525-1438. ; 18, s. 1386-1386
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Tidskriftsartikel (refereegranskat)
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| 10. |
- Borg, Sixten, et al.
(författare)
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Performance of standardized cancer patient pathways in Sweden visualized using observational data and a state-transition model
- 2023
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Ingår i: Scientific Reports. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Standardized Cancer Patient Pathways (CPPs) were introduced in Swedish healthcare starting in 2015 to improve diagnostics for patients with symptoms of cancer, patient satisfaction and equity of care between healthcare providers. An inclusion target and a time target were set. Our primary aim was to visualize the patient population going through CPPs, in terms of investigation time and indications of the various outcomes including cancer diagnoses. Our secondary aims were to examine if targets were met, and to examine frequencies of undetected cancer. We collected data from 19,204 patients starting in a CPP, and 7895 patients diagnosed with cancer in 2018 in a region of Sweden. A state transition model was developed and used as analytical framework, and patients were mapped over time in the states of the model. Visualization of the patient-flow through the model illustrates speed of investigation, time to treatment, frequencies of detected and undetected cancer. Twelve CPPs out of 28 met the inclusion target, five met the time target. After suspicion of cancer rejected, 0.8% of patients were diagnosed with the primarily suspected cancer, 1.0% with another cancer. In patients not meeting the criteria for well-founded suspicion less than 3% were later diagnosed with cancer. The visualization of the patient flow into and through standardized cancer patient pathways illustrates investigation time, events occurring and outcomes. The use of standardized cancer patient pathways detects cancer efficiently.
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