| 1. |
- Buunen, M, et al.
(författare)
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COLOR II. A randomized clinical trial comparing laparoscopic and open surgery for rectal cancer.
- 2009
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Ingår i: Danish medical bulletin. - 1603-9629 .- 0907-8916. ; 56:2, s. 89-91
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Laparoscopic resection of rectal cancer has been proven efficacious but morbidity and oncological outcome need to be investigated in a randomized clinical trial. Trial design: Non-inferiority randomized clinical trial. METHODS: The COLOR II trial is an ongoing international randomized clinical trial. Currently 27 hospitals from Europe, South Korea and Canada are including patients. The primary endpoint is loco-regional recurrence rate three years post-operatively. Secondary endpoints cover quality of life, overall and disease free survival, post-operative morbidity and health economy analysis. RESULTS: By July 2008, 27 hospitals from the Netherlands, Belgium, Germany, Sweden, Spain, Denmark, South Korea and Canada had included 739 patients. The intra-operative conversion rate in the laparoscopic group was 17%. Distribution of age, location of the tumor and radiotherapy were equal in both treatment groups. Most tumors are located in the mid-rectum (41%). CONCLUSION: Laparoscopic surgery in the treatment of rectal cancer is feasible. The results and safety of laparoscopic surgery in the treatment of rectal cancer remain unknown, but are subject of interim analysis within the COLOR II trial. Completion of inclusion is expected by the end of 2009. Trial registration: Clinicaltrials.gov, identifier: NCT00297791 (www.clinicaltrials.gov).
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| 2. |
- Gustafsson Asting, Annika, et al.
(författare)
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EP1-4 subtype, COX and PPAR gamma receptor expression in colorectal cancer in prediction of disease-specific mortality
- 2007
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Ingår i: International journal of cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 121:2, s. 232-40
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Tidskriftsartikel (refereegranskat)abstract
- The importance of prostaglandins in tumor growth and progression is well recognized, including antineoplastic activities by cyclooxygenase (COX) inhibitors. Variation in treatment response to COX inhibition has questioned differences in expression of cell surface and nuclear membrane receptors among tumors with different disease progression. The purpose of this study was to evaluate whether EP(1-4) subtype, PPAR gamma receptor and COX-1/COX-2 expression in colorectal cancer are related to tumor-specific mortality. Reverse transcription-polymerase chain reaction and immunohistochemistry were used to demonstrate expression and protein appearance in tumor tissue compared with normal colon tissue. EP(1) and EP(2) subtype receptor protein was highly present in tumor cells, EP(3) occurred occasionally and EP(4) was not visible. PPAR gamma, EP(2) and EP(4) mRNA were significantly higher in normal colon tissue compared with tumor tissue, without any distinct relationship to Dukes A-D tumor stage. Multivariate analyses indicated that increased tumor tissue EP(2) and COX-2 expression predicted poor survival (p<0.001). COX-1 expression was significantly higher than COX-2 expression in normal colon tissue. Average COX-2 mRNA was not increased in tumor tissue compared with normal colon. However, most tumor cells stained positive for COX-2 protein, which was low or undetectable in normal mucosa cells. COX-1 protein was preferentially visible in stroma. EP(1-4) subtype receptor mRNAs were generally positively correlated to both COX-1 and COX-2 in tumor tissue, but not in normal colon. Our results imply that both prostaglandin production (COX-2) and signaling via EP(1-4) subtype receptors, particularly EP(2), predict disease-specific mortality in colorectal cancer.
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| 3. |
- Gustafsson Asting, Annika, et al.
(författare)
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Genetic Copy Number Variations in Colon Mucosa Indicating Risk for Colorectal Cancer.
- 2014
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Ingår i: Journal of Cancer Therapy. - : Scientific Research Publishing, Inc.. - 2151-1934 .- 2151-1942. ; 5:14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sporadic colorectal tumors probably carry genetic alterations that may be related to familiar clusters according to risk loci visualized by SNP arrays on normal tissues. The aim of the present study was therefore to search for DNA regions (copy number variations, CNVs) as biomarkers associated to genetic susceptibility for early risk predictions of colorectal cancer. Such sequence alterations could provide additional information on phenotypic grouping of patients. Material and Methods: High resolution 105K oligonucleotide microarrays were used in search for CNV loci in DNA from tumor-free colon mucosa at primary operations for colon cancer in 60 unselected patients in comparison to DNA in buffy coat cells from 44 confirmed tumor-free and healthy blood donors. Array-detected CNVs were confirmed by Multiplex ligation-dependent probe amplification (MLPA). Results: A total number of 205 potential CNVs were present in DNA from colon mucosa. 184 (90%) of the 205 potential CNVs had been identified earlier in mucosa DNA from healthy individuals as reported to the Database of Genomic Variants. Remaining 21 (10%) CNVs were potentially novel sites. Two CNVs (3q23 and 10q21.1) were significantly related to colon cancer, but not confirmed in buffy coat DNA from the cancer patients. Conclusion: Our study reveals two CNVs that indicate increased risk for colon cancer; these DNA alterations may have been acquired by colon stem cells with subsequent appearance among epithelial mucosa cells. Impact: Certain mucosa CNV alterations may indicate individual susceptibility for malignant transformation in relationship to intestinal toxins and bacterial growth.
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| 4. |
- Gustafsson Asting, Annika, et al.
(författare)
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Prostanoid receptor expression in colorectal cancer related to tumor stage, differentiation and progression.
- 2007
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Ingår i: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 46:8, s. 1107-12
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Alterations in eicosanoid metabolism is well established in a variety of malignant tumors, particularly colorectal carcinoma. Recent studies in our laboratory have emphasized a role for EP subtype receptors in progression of colorectal cancer and disease specific mortality. Therefore, the aim of the present study was to extend our knowledge to include additional receptor expression (DP1, DP2, FP, IP, TP) for prostanoids (PGD2, TXA2, PGF2alpha, PGI2) in relationship to tumor stage, differentiation and progression of colorectal cancer. MATERIAL AND METHODS: Total RNA from 62 tumors and adjacent normal colon tissue (n = 48) was extracted. Quantification of receptor expression was performed by realtime PCR and related to the expression of an appropriate housekeeping gene (GAPDH). Tumors were assessed according to Dukes A-D (stage I-IV). RESULTS: DP1, DP2, FP and IP receptor subtypes displayed significantly reduced overall expression in tumor tissue compared to normal colon tissue, while the TP receptor subtype showed significantly higher expression in tumor tissue. Overall expression of the prostanoid receptors in tumor tissue was not related to clinical indexes as tumor stage and tumor cell differentiation evaluated by multivariate analyses. Cultured colorectal cancer cell lines with low (HT-29) and high (HCA-7) intrinsic PGE2 production at confluent state did not express DP1 and IP receptor subtypes, but displayed low expression of DP2, FP and TP receptor subtypes. CONCLUSION: The results in the present study indicate imbalanced expression of prostanoid receptors in colorectal cancer compared to normal colon tissue without clear cut relationship to disease progression. Therefore, future studies should be performed on defined cells within the tumor tissue compartment determining whether any prostanoid receptor(s) is useful as a molecular target in treatment or prevention of colorectal cancer.
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| 5. |
- Janson, Martin, et al.
(författare)
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Analysis of patient selection and external validity in the Swedish contribution to the COLOR trial.
- 2009
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Ingår i: Surgical endoscopy. - : Springer Science and Business Media LLC. - 1432-2218 .- 0930-2794. ; 23:8, s. 1764-9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The colon cancer laparoscopic or open resection (COLOR) trial is an international, randomised controlled trial comparing outcomes of open and laparoscopic surgery for colon cancer. The main purpose of this study was to determine representability by comparing included and nonincluded patients in the participating Swedish centres. DESIGN: At eight centres, which included 391 of the 422 Swedish patients, a local database search was performed to identify retrospectively all patients (n = 2,384) who underwent surgery for colon cancer during the inclusion period, and data was retrieved from medical records. RESULTS: Four hundred fifty-six patients were randomised, 65 of whom were excluded post randomisation (group 2), leaving 391 patients in the study (group 1). For 1,566 patients, valid exclusion criteria were found (group 3). Thus, 362 patients were eligible but not included (group 4). Relative to group 1, patients in group 4 had a significantly higher American Society of Anaesthesiologists (ASA) score, more advanced tumour stage and difference regarding the resections performed. Results showed that 1470 patients (62%) could be calculated as feasible for laparoscopic colon resection (LCR) in a clinical, nontrial situation. CONCLUSIONS: The study population in the Swedish part of the COLOR trial was representative of the eligible population with the exception of comorbidity, where those actually included had less severe comorbidity than the nonincluded but eligible patients. In Sweden, 50-60% of colon cancer patients can be operated on by laparoscopy.
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| 6. |
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| 7. |
- Lagerstedt, Kristina, 1976, et al.
(författare)
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Genes with relevance for early to late progression of colon carcinoma based on combined genomic and transcriptomic information from the same patients.
- 2010
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Ingår i: Cancer informatics. - 1176-9351. ; 9, s. 79-91
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Genetic and epigenetic alterations in colorectal cancer are numerous. However, it is difficult to judge whether such changes are primary or secondary to the appearance and progression of tumors. Therefore, the aim of the present study was to identify altered DNA regions with significant covariation to transcription alterations along colon cancer progression. METHODS: Tumor and normal colon tissue were obtained at primary operations from 24 patients selected by chance. DNA, RNA and microRNAs were extracted from the same biopsy material in all individuals and analyzed by oligo-nucleotide array-based comparative genomic hybridization (CGH), mRNA- and microRNA oligo-arrays. Statistical analyses were performed to assess statistical interactions (correlations, co-variations) between DNA copy number changes and significant alterations in gene and microRNA expression using appropriate parametric and non-parametric statistics. RESULTS: Main DNA alterations were located on chromosome 7, 8, 13 and 20. Tumor DNA copy number gain increased with tumor progression, significantly related to increased gene expression. Copy number loss was not observed in Dukes A tumors. There was no significant relationship between expressed genes and tumor progression across Dukes A-D tumors; and no relationship between tumor stage and the number of microRNAs with significantly altered expression. Interaction analyses identified overall 41 genes, which discriminated early Dukes A plus B tumors from late Dukes C plus D tumor; 28 of these genes remained with correlations between genomic and transcriptomic alterations in Dukes C plus D tumors and 17 in Dukes D. One microRNA (microR-663) showed interactions with DNA alterations in all Dukes A-D tumors. CONCLUSIONS: Our modeling confirms that colon cancer progression is related to genomic instability and altered gene expression. However, early invasive tumor growth seemed rather related to transcriptomic alterations, where changes in microRNA may be an early phenomenon, and less to DNA copy number changes.
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| 8. |
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| 9. |
- Lagerstedt, Kristina, 1976, et al.
(författare)
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The role of combined allelic imbalance and mutations of p53 in tumor progression and survival following surgery for colorectal carcinoma
- 2005
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Ingår i: International journal of oncology. - 1019-6439. ; 27:6, s. 1707-15
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Tidskriftsartikel (refereegranskat)abstract
- The role of p53 mutations in disease progression and survival of colorectal cancer is unclear, since numerous studies have reported different conclusions. However, few reports, if any, have evaluated disease progression and survival in relationship to 'functional' and 'non-functional' p53 status defined by genetic and molecular indications. Malignant colorectal tumors, from 72 unselected patients who underwent primary and potentially curative elective tumor resections, were either classified as p53 functional (p53+/+, p53+/-) or non-functional (p53-/-) based on DNA sequence analysis of all p53 exons, including determination of allelic imbalance of p53 (LOH), according to four DNA markers; 2 within the coding gene and two markers in the immediate flanking regions of p53. Tumor frequency of microsatellite instability was also analyzed according to Dukes' A-D stages. Dukes' staging predicted survival as expected, while the conceptual p53 status, functional p53 vs non-functional p53, did not clear-cut predict disease specific survival. p53 mutations alone or allelic imbalance inside the reading frame of the gene were unpredictive of survival, while allelic imbalance downstream of p53 predicted reduced survival (p < 0.05). The present study demonstrates that base mutations in combination with allelic imbalance within the reading frame of p53 do not predict survival or progression of colorectal cancer, while allelic imbalance upstream coding parts of the gene predicted disease-specific survival in univariate analysis. Thus, structural alterations within the gene seem less important than alterations in regions with potential control elements.
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| 10. |
- Lagerstedt, Kristina, 1976, et al.
(författare)
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Tumor Genome Wide DNA Alterations Assessed by Array CGH in Patients with Poor and Excellent Survival Following Operation for Colorectal Cancer.
- 2007
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Ingår i: Cancer informatics. - 1176-9351. ; 3, s. 341-55
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Tidskriftsartikel (refereegranskat)abstract
- Genome wide DNA alterations were evaluated by array CGH in addition to RNA expression profiling in colorectal cancer from patients with excellent and poor survival following primary operations.DNA was used for CGH in BAC and cDNA arrays. Global RNA expression was determined by 44K arrays. DNA and RNA from tumor and normal colon were used from cancer patients grouped according to death, survival or Dukes A, B, C and D tumor stage. Confirmed DNA alterations in all Dukes A - D were judged relevant for carcinogenesis, while changes in Dukes C and D only were regarded relevant for tumor progression.Copy number gain was more common than loss in tumor tissue (p < 0.01). Major tumor DNA alterations occurred in chromosome 8, 13, 18 and 20, where short survival included gain in 8q and loss in 8p. Copy number gains related to tumor progression were most common on chromosome 7, 8, 19, 20, while corresponding major losses appeared in chromosome 8. Losses at chromosome 18 occurred in all Dukes stages. Normal colon tissue from cancer patients displayed gains in chromosome 19 and 20. Mathematical Vector analysis implied a number of BAC-clones in tumor DNA with genes of potential importance for death or survival.The genomic variation in colorectal cancer cells is tremendous and emphasizes that BAC array CGH is presently more powerful than available statistical models to discriminate DNA sequence information related to outcome. Present results suggest that a majority of DNA alterations observed in colorectal cancer are secondary to tumor progression. Therefore, it would require an immense work to distinguish primary from secondary DNA alterations behind colorectal cancer.
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