| 1. |
- Baldetorp, Bo, et al.
(författare)
-
Different calculation methods for flow cytometric S-phase fraction: prognostic implications in breast cancer? The Swedish Society of Cancer Study Group
- 1998
-
Ingår i: Cytometry. - 0196-4763. ; 33:4, s. 385-393
-
Tidskriftsartikel (refereegranskat)abstract
- S-phase fraction (SPF), estimated in the flow cytometric DNA histogram, is a prognostic factor in breast cancer. There are, however, some inherent difficulties in the estimation of SPF, such as the influence of debris, aggregates, and normal cells. Most of the available SPF calculation principles try to consider these difficulties, but so far no consensus has been reached with regard to which principle is to be recommended. The aim of the present study was to investigate the prognostic impact of SPF when estimated with different calculation methods in frozen breast cancer samples from 350 patients. Two nonparametric (Rman, Rmin/both rectangle) and three parametric (ACAS/DNA-base, ModFit, and MultiCycle) calculation methods, with and without correction for debris and aggregates, were used. The mean values for SPF varied from 4.3% (ACAS/DNA-base with correction for debris and aggregates) to 9.4% (MultiCycle without any correction for background). The pairwise correlation between methods varied considerably (R = 0.72-0.98). After categorization of SPF values into low SPF (lower two tertiles) and high SPF (upper tertile), all methods yielded statistically significant Pvalues for recurrence-free survival (median follow-up time 67 months), both univariately (0.0004-< 0.0001) and multivariately (0.048-0.0004), after adjusting for nodal status, tumor size, and estrogen receptor status. SPF with background correction did not yield lower P values than SPF without. Regardless of which method was used, SPF showed similar correlations with lymph node involvement, tumor size, and estrogen receptor content. In conclusion, as the mean value of SPF for different calculation methods varies, each laboratory must be restricted to use only one method. Background correction does not seem to improve the prognostic impact of SPF in DNA histograms. Based on the experiences obtained in the present study, S-phase calculation methods without background correction may therefore be the most suitable for routine evaluation of DNA histograms of fresh frozen breast cancer material (ModFit, MultiCycle, and Rman [the latter only for experienced operators]). The nonparametric Rmin, with an automatic setting of the region used for SPF calculation, may be an alternative, but suffers from the disadvantage of not being commercially available yet.
|
|
| 2. |
|
|
| 3. |
- Paulsson, J., et al.
(författare)
-
High expression of stromal PDGFR beta is associated with reduced benefit of tamoxifen in breast cancer
- 2017
-
Ingår i: Journal of Pathology Clinical Research. - : Wiley. - 2056-4538. ; 3:1, s. 38-43
-
Tidskriftsartikel (refereegranskat)abstract
- Cancer-associated fibroblasts (CAFs) regulate tumour growth, metastasis and response to treatment. Recent studies indicate the existence of functionally distinct CAF subsets. Suggested mechanisms whereby CAFs can impact on treatment response include paracrine signalling affecting cancer cell drug sensitivity and effects on tumour drug uptake. PDGFR beta is an important regulator of fibroblasts. Experimental studies have linked PDGFR beta-positive fibroblasts to metastasis and also to reduced tumour drug uptake. This study has investigated the potential role of PDGFR beta-positive fibroblasts in response to adjuvant tamoxifen treatment of breast cancer. Analyses of two breast cancer collections from randomised studies analysing adjuvant tamoxifen treatment in early breast cancer demonstrated significant benefit of tamoxifen in the group with low stromal PDGFR beta, which was not observed in the group with high stromal PDGFR beta. In general terms these findings provide novel evidence, derived from analyses of randomised clinical studies, of response-predictive capacity of a marker-defined subset of CAFs and, more specifically, identify stromal PDGFR beta as a marker related to tamoxifen benefit in early breast cancer.
|
|
| 4. |
- Sternby Eilard, Malin, 1974, et al.
(författare)
-
Quality of life as a prognostic factor for survival in hepatocellular carcinoma
- 2018
-
Ingår i: Liver International. - : Wiley. - 1478-3223. ; 38:5, s. 885-894
-
Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Prognostication in hepatocellular carcinoma (HCC) is demanding. Not only tumour extent and performance status are to be considered, but also liver function, which is often limiting for both survival itself and for treatment possibilities. This study was conducted to assess whether patient-reported questionnaires containing general and liver-specific questions could improve prognostication of survival. Methods: 185 patients with hepatocellular carcinoma in Norway and Sweden were prospectively included. Patients completed the quality-of-life questionnaires EORTC QLQ C30 and HCC18, and clinical, radiological and laboratory parameters were registered. Multivariate Cox regression and Harrell's C-statistics were used to identify the model that best predicted mortality. Results: Quality-of-life data were prognostic for overall survival. Fatigue and nutrition scales were prognostic in the multivariable analyses alone and in combination with clinical parameters. The prognostic value of established scoring systems was increased by the addition of QoL data. The best prognostic power was achieved by combining HCC18 nutrition scale with selected background parameters. Conclusion: Quality-of-life questionnaires can prognosticate mortality in HCC patients. When combined with established scoring systems, both the general cancer questionnaire EORTC QLQ C30, and the additional liver cancer-specific HCC18 increased the prognostic accuracy slightly.
|
|
| 5. |
|
|
| 6. |
- Busch, Susann, et al.
(författare)
-
Loss of TGF beta Receptor Type 2 Expression Impairs Estrogen Response and Confers Tamoxifen Resistance
- 2015
-
Ingår i: Cancer Research. - : American Association for Cancer Research (AACR). - 0008-5472 .- 1538-7445. ; 75:7, s. 1457-1469
-
Tidskriftsartikel (refereegranskat)abstract
- One third of the patients with estrogen receptor alpha (ER alpha)-positive breast cancer who are treated with the antiestrogen tamoxifen will either not respond to initial therapy or will develop drug resistance. Endocrine response involves crosstalk between ER alpha and TGF beta signaling, such that tamoxifen non-responsiveness or resistance in breast cancer might involve aberrant TGF beta signaling. In this study, we analyzed TGF beta receptor type 2 (TGFBR2) expression and correlated it with ER alpha status and phosphorylation in a cohort of 564 patients who had been randomized to tamoxifen or no-adjuvant treatment for invasive breast carcinoma. We also evaluated an additional four independent genetic datasets in invasive breast cancer. In all the cohorts we analyzed, we documented an association of low TGFBR2 protein and mRNA expression with tamoxifen resistance. Functional investigations confirmed that cell cycle or apoptosis responses to estrogen or tamoxifen in ER alpha-positive breast cancer cells were impaired by TGFBR2 silencing, as was ER alpha phosphorylation, tamoxifen-induced transcriptional activation of TGF beta, and upregulation of the multidrug resistance protein ABCG2. Acquisition of low TGFBR2 expression as a contributing factor to endocrine resistance was validated prospectively in a tamoxifen-resistant cell line generated by long-term drug treatment. Collectively, our results established a central contribution of TGF beta signaling in endocrine resistance in breast cancer and offered evidence that TGFBR2 can serve as an independent biomarker to predict treatment outcomes in ER alpha-positive forms of this disease. (C)2015 AACR.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
- Enberg, Rikard, et al.
(författare)
-
Enhancement of associated (HW -/+)-W-+/- production in the NMSSM
- 2012
-
Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368 .- 1550-7998. ; 85:7
-
Tidskriftsartikel (refereegranskat)abstract
- We study the associated production of a charged Higgs and a W boson in high-energy pp collisions at the LHC. This is an interesting process for charged Higgs discovery, or exclusion, since the production cross section could depend strongly on the model, offering potential discriminating power between supersymmetric extensions of the standard model with minimal or extended Higgs sectors. We compute the cross section for this process in the next-to-minimal supersymmetric standard model (NMSSM), at the tree level for quark-quark scattering, and at one-loop level for gluon-gluon scattering. The most important corrections beyond leading order are taken into account using an improved Born approximation. We find that the pp -> (HW -/+)-W-+/- cross section can be resonantly enhanced by up to an order of magnitude over its MSSM value (both for root s = 7 TeV and 14 TeV) through the contributions of heavy, neutral, singlet-dominated Higgs bosons appearing in the s-channel. Since such Higgs mass configurations are normally not possible in the MSSM, the observation of associated (HW -/+)-W-+/- production at the LHC could provide a striking, although indirect, signature of a more complicated Higgs sector.
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
- Hagstrom, H, et al.
(författare)
-
Steatohepatitis Is Not Associated with an Increased Risk for Fibrosis Progression in Nonalcoholic Fatty Liver Disease
- 2018
-
Ingår i: Gastroenterology research and practice. - : Hindawi Limited. - 1687-6121 .- 1687-630X. ; 2018, s. 1942648-
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction. Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease globally. The majority of NAFLD patients have fatty liver without inflammation (nonalcoholic fatty liver, NAFL), whereas a minority develop steatohepatitis (nonalcoholic steatohepatitis, NASH). Only NASH and not NAFL has been considered to increase the risk for fibrosis progression. The present study investigates risk factors for fibrosis progression in patients with NAFLD, and if fibrosis progression associates with subsequent mortality. Material and Methods. All patients with at least two liver biopsies more than a year apart at our hospital between 1971 and 2016 were identified. Data on plausible risk factors for fibrosis progression were collected. Biopsies were scored for the presence of NASH and fibrosis stage. Regression models were used to investigate the association between baseline NASH and fibrosis progression and fibrosis progression with future mortality. Results. 60 patients had undergone serial biopsies (median interval between biopsies 8.4 years, range 1–33 years), with 26 patients (43%) having fibrosis progression. We found no significant risk factors for progression of fibrosis except time between biopsies. Among patients with fibrosis progression, 54% had NAFL and 46% had NASH at baseline. There was a trend for an association between fibrosis progression per se and increased mortality (hazard ratio 2.83, 95% CI 1.0–8.1, p=0.05). Conclusions. In this study on NAFLD, baseline steatohepatitis was not associated with an increased risk for fibrosis progression. NAFLD patients without steatohepatitis may develop progressive fibrosis, and those with progressive fibrosis appear to have a higher mortality risk irrespective of baseline NASH status.
|
|
| 19. |
|
|
| 20. |
- Holmer, M, et al.
(författare)
-
Associations between subcutaneous adipocyte hypertrophy and nonalcoholic fatty liver disease
- 2022
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1, s. 20519-
-
Tidskriftsartikel (refereegranskat)abstract
- Adipocyte hypertrophy and expression of adipokines in subcutaneous adipose tissue (SAT) have been linked to steatosis, nonalcoholic steatohepatitis (NASH) and fibrosis in morbidly obese (BMI ≥ 40 kg/m2) subjects. It is unknown if this is also true for subjects with NAFLD with lesser degrees of obesity (BMI < 35 kg/m2). Thirty-two subjects with biopsy-proven NAFLD and 15 non-diabetic controls matched for BMI underwent fine-needle biopsies of SAT. Adipocyte volume was calculated. RNA-sequencing of SAT was performed in a subset of 20 NAFLD patients. Adipocyte volume and gene expression levels were correlated to the presence of NASH or significant fibrosis. Subjects with NAFLD had larger adipocyte volume compared with controls, (1939 pL, 95% CI 1130–1662 vs. 854 pL, 95% CI 781–926, p < 0.001). There was no association between adipocyte volume and the presence of NASH. Gene expression of adipokines previously described to correlate with NASH in morbid obesity, was not associated with NASH or fibrosis. Our results suggest that persons with NAFLD have larger SAT adipocytes compared with controls and that adipocytes are involved in the pathophysiology of hepatic steatosis in NAFLD. However, adipocyte volume was not associated with NASH or fibrosis in NAFLD subjects with varying degrees of obesity.
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
- Johansson, A., et al.
(författare)
-
Twenty-Year Benefit From Adjuvant Goserelin and Tamoxifen in Premenopausal Patients With Breast Cancer in a Controlled Randomized Clinical Trial
- 2022
-
Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 40:35, s. 4071-4082
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSETo assess the long-term (20-year) endocrine therapy benefit in premenopausal patients with breast cancer.METHODSSecondary analysis of the Stockholm trial (STO-5, 1990-1997) randomly assigning 924 premenopausal patients to 2 years of goserelin (3.6 mg subcutaneously once every 28 days), tamoxifen (40 mg orally once daily), combined goserelin and tamoxifen, or no adjuvant endocrine therapy (control) is performed. Random assignment was stratified by lymph node status; lymph node-positive patients (n = 459) were allocated to standard chemotherapy (cyclophosphamide, methotrexate, and fluorouracil). Primary tumor immunohistochemistry (n = 731) and gene expression profiling (n = 586) were conducted in 2020. The 70-gene signature identified genomic low-risk and high-risk patients. Kaplan-Meier analysis, multivariable Cox proportional hazard regression, and multivariable time-varying flexible parametric modeling assessed the long-term distant recurrence-free interval (DRFI). Swedish high-quality registries allowed a complete follow-up of 20 years.RESULTSIn estrogen receptor-positive patients (n = 584, median age 47 years), goserelin, tamoxifen, and the combination significantly improved long-term distant recurrence-free interval compared with control (multivariable hazard ratio [HR], 0.49; 95% CI, 0.32 to 0.75, HR, 0.57; 95% CI, 0.38 to 0.87, and HR, 0.63; 95% CI, 0.42 to 0.94, respectively). Significant goserelin-tamoxifen interaction was observed (P = .016). Genomic low-risk patients (n = 305) significantly benefitted from tamoxifen (HR, 0.24; 95% CI, 0.10 to 0.60), and genomic high-risk patients (n = 158) from goserelin (HR, 0.24; 95% CI, 0.10 to 0.54). Increased risk from the addition of tamoxifen to goserelin was seen in genomic high-risk patients (HR, 3.36; 95% CI, 1.39 to 8.07). Moreover, long-lasting 20-year tamoxifen benefit was seen in genomic low-risk patients, whereas genomic high-risk patients had early goserelin benefit.CONCLUSIONThis study shows 20-year benefit from 2 years of adjuvant endocrine therapy in estrogen receptor-positive premenopausal patients and suggests differential treatment benefit on the basis of tumor genomic characteristics. Combined goserelin and tamoxifen therapy showed no benefit over single treatment. Long-term follow-up to assess treatment benefit is critical.
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
|
|
| 30. |
|
|
| 31. |
|
|
| 32. |
|
|
| 33. |
|
|
| 34. |
- Mollbrink, A, et al.
(författare)
-
Expression of thioredoxins and glutaredoxins in human hepatocellular carcinoma: correlation to cell proliferation, tumor size and metabolic syndrome
- 2014
-
Ingår i: International journal of immunopathology and pharmacology. - : SAGE Publications. - 0394-6320 .- 2058-7384. ; 27:2, s. 169-183
-
Tidskriftsartikel (refereegranskat)abstract
- Thioredoxins (Trx) and glutaredoxins (Grx) are thiol oxidoreductases that are ubiquitously expressed, and are involved in several biological processes. The expression of thioredoxins and glutaredoxins is induced in many neoplasms, and correlates with prognosis in gallbladder and colorectal carcinoma. The aim of the present study was to examine the expression pattern of these proteins (redoxins) in hepatocellular carcinoma (HCC) and to correlate their levels with clinical features. Paraffin-embedded tissues from 25 patients resected for HCC and 15 patients resected for colorectal carcinoma (CRC) liver metastases were analyzed with immunohistochemistry. Our results showed that Trx1, Trx2 and Grx5 were upregulated in HCCs as compared to the respective surrounding liver. In comparison, almost all redoxins were upregulated in CRC liver metastases, with Trx1 and Grx3 being significantly more increased in the CRC liver metastases than in the primary HCC tumors. In HCC, Trx1 correlated significantly with cell proliferation, and with a trend towards increased levels with micro-vascular invasion, while expression of Trx2 decreased with tumor size. Trx1 levels were lower in tumors of males, smokers, and patients with high alcohol consumption. Grx2 levels were significantly higher in patients with metabolic syndrome. In conclusion, this study illustrates specific correlations of individual redoxins to clinical features of HCC, and implicates the redoxins in the pathogenesis of HCC.
|
|
| 35. |
|
|
| 36. |
- Risberg, B, et al.
(författare)
-
Inter-institutional reproducibility of flow cytometric DNA-analysis in breast carcinomas
- 1994
-
Ingår i: Analytical Cellular Pathology. - 0921-8912. ; 6:1, s. 23-36
-
Tidskriftsartikel (refereegranskat)abstract
- In order to study interinstitutional reproducibility of flow cytometric DNA-analysis (DNA-FCM), frozen pieces from 30 consecutive breast carcinomas were analysed by 5 laboratories. Different instruments, preparation and DNA staining methods were used. A concordance in DNA-ploidy status was obtained in 26 of the 30 tumours. The discrepancy can mainly be explained by intratumoural DNA-heterogeneity since a complete agreement in ploidy status was obtained when four of the laboratories analysed the same cell suspension, where solid bits showed differing results. The sampling method seems therefore to be a crucial step for the results and needs further studies. As far as the estimation of S-phase fraction was concerned, one laboratory obtained significantly higher values compared to the other four. The correlation between the other four laboratories varied between r = 0.66-0.92.
|
|
| 37. |
|
|
| 38. |
|
|
| 39. |
|
|
| 40. |
|
|
| 41. |
|
|
| 42. |
|
|
| 43. |
|
|
| 44. |
|
|
| 45. |
|
|
| 46. |
|
|
