| 1. |
- Devarakonda, Sravani, et al.
(författare)
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Low-grade intestinal inflammation two decades after pelvic radiotherapy.
- 2023
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Ingår i: EBioMedicine. - 2352-3964. ; 94
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Tidskriftsartikel (refereegranskat)abstract
- Radiotherapy is effective in the treatment of cancer but also causes damage to non-cancerous tissue. Pelvic radiotherapy may produce chronic and debilitating bowel symptoms, yet the underlying pathophysiology is still undefined. Most notably, although pelvic radiotherapy causes an acute intestinal inflammation there is no consensus on whether the late-phase pathophysiology contains an inflammatory component or not. To address this knowledge gap, we examined the potential presence of a chronic inflammation in mucosal biopsies from irradiated pelvic cancer survivors.We biopsied 24 cancer survivors two to 20 years after pelvic radiotherapy, and four non-irradiated controls. Using tandem mass tag (TMT) mass spectrometry and mRNA sequencing (mRNA-seq), we charted proteomic and transcriptomic profiles of the mucosal tissue previously exposed to a high or a low/no dose of radiation. Changes in the immune cell populations were determined with flow cytometry. The integrity of the protective mucus layers were determined by permeability analysis and 16S rRNA bacterial detection.942 proteins were differentially expressed in mucosa previously exposed to a high radiation dose compared to a low radiation dose. The data suggested a chronic low-grade inflammation with neutrophil activity, which was confirmed by mRNA-seq and flow cytometry and further supported by findings of a weakened mucus barrier with bacterial infiltration.Our results challenge the idea that pelvic radiotherapy causes an acute intestinal inflammation that either heals or turns fibrotic without progression to chronic inflammation. This provides a rationale for exploring novel strategies to mitigate chronic bowel symptoms in pelvic cancer survivors.This study was supported by the King Gustav V Jubilee Clinic Cancer Foundation (CB), The Adlerbertska Research Foundation (CB), The Swedish Cancer Society (GS), The Swedish State under the ALF agreement (GS and CB), Mary von Sydow's foundation (MA and VP).
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| 2. |
- Gripeteg, Lena, 1970, et al.
(författare)
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Concomitant Associations of Healthy Food Intake and Cardiorespiratory Fitness With Coronary Artery Calcium
- 2018
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149 .- 1879-1913. ; 122:4, s. 560-564
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Tidskriftsartikel (refereegranskat)abstract
- Conflicting findings remain regarding associations between lifestyle behaviors and coronary artery calcium (CAC). We investigated concomitant associations of healthy food intake and cardiorespiratory fitness (CRF) with CAC. Data from 706 men and women 50 to 64 years old from the Swedish SCAPIS pilot trial were analyzed. A CAC score was calculated using the Agatston method. A Healthy Food Index (HFI) was established using data from a web-based food frequency questionnaire. CRF was assessed from a bike exercise test. Regression analyses were performed with occurrence of CAC (dichotomous) and level of CAC score in patients with CAC (continuous) as outcomes. 58% had 0 CAC score. HFI was significantly associated with having no CAC (standardized coefficient β = 0.18, p <0.001) but not with level of CAC score (β = −0.09, p = 0.34). CRF showed no significant association with having no CAC (β = −0.08, p = 0.12) or with the level of CAC score (β = −0.04, p = 0.64). However, there was an interaction between HFI and CRF (β = −0.23, p = 0.02); for increasing levels of CRF there was stronger negative association between HFI and level of CAC score, reaching β = −0.48, p = 0.045 for the highest CRF level. In conclusion, these results emphasize the importance of a healthy food intake in combination with higher CRF to counteract CAC development.
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| 3. |
- Hardling, Mats, et al.
(författare)
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Serial monitoring of BCR-ABL transcripts in chronic myelogenous leukemia (CML) treated with imatinib mesylate
- 2004
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Ingår i: Med Oncol. - 1357-0560. ; 21:4, s. 349-58
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Tidskriftsartikel (refereegranskat)abstract
- Survival among chronic myelogenous leukemia (CML) patients can be linked to the reduction in leukemic cell burden. Treatment with imatinib mesylate results in a high frequency of complete cytogenetic response, which can be further stratified using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). We have serially monitored peripheral blood and bone marrow BCR-ABL transcripts using qRT-PCR in CML patients commencing imatinib therapy, and compared the results with bone marrow cytogenetics. Seventeen patients (aged 25-74 yr) with Philadelphia chromosome positive CML in first chronic phase were treated with imatinib targeting a dose of 400 mg/d. The median follow up is 30 mo (range 9-33 mo). Every third month the product of the BCR-ABL fusion gene was evaluated in both blood and bone marrow specimens by real-time RT-PCR using the TaqMan probe system. In 113 simultaneously obtained blood and bone marrow samples, the BCR-ABL transcript values agreed well with cytogenetic data. Blood and bone marrow specimens gave comparable values for BCR-ABL transcripts. Before start of imatinib therapy there was a considerable variation in BCR-ABL transcripts among the patients, ranging approximately one log (base 10). Similarly, patients with a complete cytogenetic response following imatinib therapy had variable BCR-ABL transcript levels, ranging at least three logs (base 10). The major decline in BCR-ABL transcripts occurred within 6 mo after start of imatinib therapy. The decline in BCR-ABL transcripts, following imatinib therapy, appears to level off at 12-15 mo. Two late responders were identified with a still decreasing level in BCR-ABL transcripts after 24 mo of treatment. It is concluded that BCR-ABL mRNA quantification in peripheral blood is suitable for routine monitoring of the response to treatment and long-term disease status in CML, especially in patients who have achieved a complete cytogenetic response. A plateau in BCR-ABL transcripts seems to have been reached after 12-15 mo of imatinib treatment; however, some "late responders" are seen.
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| 4. |
- Ngia, Lester S.H. 1965, et al.
(författare)
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Adaptive neural nets filter using a recursive Levenberg-Marquardt search direction
- 1998
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Ingår i: Proc. Asilomar Conf. Signals, Systems, Computers, 01 Nov 1998-04 Nov 1998. ; 1, s. 697-701
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Konferensbidrag (refereegranskat)abstract
- This paper proposes a recursive Levenberg-Marquardt (LM) search direction as the training algorithm for non-linear adaptive filters, which use multi-layer feed forward neural nets as the filter structures. The neural nets can be considered as a class of non-linear adaptive filters with transversal or recursive filter structures. In the off-line training, the LM method is regarded as an intermediate method between the steepest descent (SD) and Gauss-Newton (GN) methods, and it has better convergence properties than the other two methods. In the echo cancellation experiments, the recursive LM algorithm converges faster and gives higher echo return loss enhancement (ERLE) than the recursive SD and GN algorithms.
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| 5. |
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| 6. |
- Sjöberg, Mats, 1965-, et al.
(författare)
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Infliximab or cyclosporine as rescue therapy in hospitalized patients with steroid-refractory ulcerative colitis : a retrospective observational study
- 2012
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Ingår i: Inflammatory Bowel Diseases. - : John Wiley & Sons. - 1078-0998 .- 1536-4844. ; 18:2, s. 212-218
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cyclosporine (CsA) or infliximab (IFX) are used as rescue therapies in steroid-refractory, severe attacks of ulcerative colitis (UC). There are no data comparing the efficacy of these two alternatives. Methods: Outcome of rescue therapy was retrospectively studied in two cohorts of patients hospitalized due to steroid-refractory moderate to severe UC: 1) a Swedish-Danish cohort (n 49) treated with a single infusion of IFX; 2) an Austrian cohort (n 43) treated with intravenous CsA. After successful rescue therapy, maintenance immunomodulator treatment was given to 27/33 (82%) of IFX patients and to 31/40 (78%) of CsA patients. Endpoints were colectomy-free survival at 3 and 12 months. Kaplan-Meier and Cox regression models were used to evaluate the association between treatment groups and colectomy. Results: At 15 days, colectomy-free survival in the IFX cohort was 36/49 (73%) versus 41/43 (95%) in the CsA cohort (P = 0.005), at 3 months 33/49 (67%) versus 40/43 (93%) (P = 0.002), and at 12 months 28/49 (57%) versus 33/43 (77%) (P = 0.034). After adjusting for potential confounding factors, Cox regression analysis yielded adjusted hazard ratios for risk of colectomy in IFX-treated patients of 11.2 (95% confidence interval [CI] 2.4-53.1, P = 0.002) at 3 months and of 3.0 (95% CI 1.1-8.2, P = 0.030) at 12 months in comparison with CsA-treated patients. There were no opportunistic infections or mortality. Conclusions: Colectomy frequencies were significantly lower after rescue therapy with CsA than with a single infusion of IFX both at 3 and 12 months' follow-up. The superiority of CsA was seen principally during the first 15 days.
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