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  • Andreasson, Håkan, et al. (författare)
  • Histopathological Classification of Pseudomyxoma Peritonei and the Prognostic Importance of PINCH Protein
  • 2012
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 32:4, s. 1443-1448
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim:The aims of this study were i) to assess a new and more detailed histopathological classification and to analyze concordance between pathologists in the histopathological classification of pseudomyxoma peritonei (PMP); ii) to analyze the expression in the stroma of the particularly interesting new cysteine-histidine (PINCH) protein and its prognostic importance in PMP.Materials and Methods:Surgical specimens from 81 patients, classified according to the Ronnett et al histopathological classification were compared to a new system with four groups ranging from indolent to aggressive growth patterns. PINCH protein expression was analyzed and was related to clinical variables.Results:The new four-group classification provided better prognostic information than the classification according to Ronnett et al. (p=0.04). Expression of the PINCH protein in the stroma was found in 83% of the cases and was associated with high tumor burden (p=0.002) and a poor prognosis (p=0.04).Conclusion:The proposed new PMP classification system may provide additional prognostic information. PINCH protein is expressed in PMP and has prognostic information.
  • Andréasson, Håkan, et al. (författare)
  • Outcome differences between debulking surgery and cytoreductive surgery in patients with pseudomyxoma peritonei
  • 2012
  • Ingår i: European Journal of Surgical Oncology. - 0748-7983 .- 1532-2157. ; 38:10, s. 962-968
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:The aim of this study was to compare debulking surgery and cytoreductive surgery (CRS) in patients with Pseudomyxoma peritonei (PMP) regarding efficacy and safety.PATIENTS AND METHODS:Data were extracted from medical records and treatment outcomes were analyzed for all 152 patients with PMP who were scheduled for debulking surgery and intraperitoneal chemotherapy (IPC) or CRS and IPC at Uppsala University Hospital, Uppsala, Sweden, between September 1993 and December 2008.RESULTS:One hundred and ten patients (73%) were treated with CRS and IPC and 40 (27%) with debulking surgery and IPC. In two patients (1%), surgery was defined as open and close. Patients with CRS and IPC had a 74% 5-year overall survival (OS) rate compared with 40% for those treated with debulking surgery (P < 0.001). Patients with no residual macroscopic tumour (R1 resection) had a better 5-year OS rate of 94% compared with 28% for patients with macroscopic residual tumour (R2) (P < 0.001). Grades II-IV adverse events were seen in 29% of debulked patients and in 47% of CRS/IPC patients (P = 0.053).CONCLUSIONS:CRS and IPC seems more efficient than debulking surgery and IPC but with numerically higher morbidity. Therefore, if surgically possible, CRS should be the treatment of choice for PMP patients. However, debulking surgery may still be of benefit to selected patients for palliative purposes.
  • Anney, Richard, et al. (författare)
  • A genome-wide scan for common alleles affecting risk for autism.
  • 2010
  • Ingår i: Human Molecular Genetics. - 0964-6906. ; 19:20, s. 4072-4082
  • Tidskriftsartikel (refereegranskat)abstract
    • Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
  • Anney, Richard, et al. (författare)
  • Individual common variants exert weak effects on the risk for autism spectrum disorders.
  • 2012
  • Ingår i: Human Molecular Genetics. - 0964-6906. ; 21:21, s. 4781-92
  • Tidskriftsartikel (refereegranskat)abstract
    • While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASD), the contribution of common variation to ASD risk is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating association of individual SNPs, we also sought evidence that common variants, en masse, might affect risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest p-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. By contrast, allele-scores derived from the transmission of common alleles to Stage 1 cases significantly predict case-status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele-score results, it is reasonable to conclude that common variants affect ASD risk but their individual effects are modest.
  • Bang, Peter, et al. (författare)
  • Free dissociable IGF-I : Association with changes in IGFBP-3 proteolysis and insulin sensitivity after surgery
  • 2016
  • Ingår i: Clinical Nutrition. - Churchill Livingstone. - 0261-5614. ; 35:2, s. 408-413
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Patients receiving a carbohydrate drink (CHO) before major abdominal surgery display improved insulin sensitivity postoperatively and increased proteolysis of IGFBP-3 (IGFBP-3-PA) compared to patients undergoing similar surgery after overnight fasting. Aims: We hypothesized that serum IGFBP-3-PA increases bioavailability of circulating IGF-I and preserves insulin sensitivity in patients given CHO. Design: Matched control study. Methods: At Karolinska University Hospital, patients given CHO before major elective abdominal surgery (CHO,n = 8) were compared to patients undergoing similar surgical procedures after overnight fasting (FAST,n = 10). Results from two different techniques for determination of free-dissociable IGF-I (fdIGF-I) were compared with changes in IGFBP-3-PA and insulin sensitivity. Results: Postoperatively, CHO displayed 18% improvement in insulin sensitivity (hyperinsulinemic clamp) and increased IGFBP-3-PA vs. FAST. As determined by IRMA, fdIGF-I increased by 48 +/- 25% in CHO while fdIGF-I decreased by 13 +/- 18% in FAST (p &lt; 0.01 vs. CHO, when corrected for duration of surgery). However, fdIGF-I determined by ultra-filtration decreased similarly in both groups (-22 +/- 8% vs. -25 +/- 8%, p = 0.8) and IGFBP-1 increased similarly in both groups. Patients with less insulin resistance after surgery demonstrated larger increases in fdIGF-I by IRMA (r = 0.58, p &lt; 0.05). Fifty-three % of the variability of the changes in fdIGF-I by IRMA could be explained by changes in IGFBP-3-PA and total IGF-I levels (p &lt; 0.05), while IGFBP-1 did not contribute significantly. Conclusion: During conditions when serum IGF-I bioavailability is regulated by IGFBP-3 proteolysis, measurements of fdIGF-I by IRMA is of physiological relevance as it correlates with the associated changes in insulin sensitivity.
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