| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Mingardo, E, et al.
(author)
-
A genome-wide association study with tissue transcriptomics identifies genetic drivers for classic bladder exstrophy
- 2022
-
In: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 1203-
-
Journal article (peer-reviewed)abstract
- Classic bladder exstrophy represents the most severe end of all human congenital anomalies of the kidney and urinary tract and is associated with bladder cancer susceptibility. Previous genetic studies identified one locus to be involved in classic bladder exstrophy, but were limited to a restrict number of cohort. Here we show the largest classic bladder exstrophy genome-wide association analysis to date where we identify eight genome-wide significant loci, seven of which are novel. In these regions reside ten coding and four non-coding genes. Among the coding genes is EFNA1, strongly expressed in mouse embryonic genital tubercle, urethra, and primitive bladder. Re-sequence of EFNA1 in the investigated classic bladder exstrophy cohort of our study displays an enrichment of rare protein altering variants. We show that all coding genes are expressed and/or significantly regulated in both mouse and human embryonic developmental bladder stages. Furthermore, nine of the coding genes residing in the regions of genome-wide significance are differentially expressed in bladder cancers. Our data suggest genetic drivers for classic bladder exstrophy, as well as a possible role for these drivers to relevant bladder cancer susceptibility.
|
|
| 5. |
|
|
| 6. |
- Svedman, F. C., et al.
(author)
-
Plasma Thymidine Kinase Activity as a Novel Biomarker in Metastatic Melanoma Patients Treated with Immune Checkpoint Inhibitors
- 2022
-
In: Cancers. - : MDPI AG. - 2072-6694. ; 14:3
-
Journal article (peer-reviewed)abstract
- Background. Immune checkpoint inhibitors (ICI) are effective in fractions of patients with disseminated melanoma. This study is the first to analyze the plasma activity of thymidine kinase (TK), an enzyme involved in DNA synthesis and repair, as a biomarker in melanoma patients. Meth-ods. Plasma samples were collected prior to treatment start in patients with unresectable metastatic cutaneous melanoma, treated with ICI (anti-CTLA-4 and/or anti-PD-1). Plasma TK activity (TKa) levels were determined using the DiviTum TKa ELISA assay. TKa levels were correlated with patients’ baseline characteristics, response rate (RR), progression-free survival (PFS), and overall survival (OS). Results. In the 90 study patients, the median TKa level was 42 Du/L (range <20–1787 Du/L). A significantly higher plasma TKa was found in patients with ECOG performance status ≥1 (p = 0.003), M1c-d disease (p = 0.015), and elevated lactate dehydrogenase levels (p < 0.001). The RR was 63.2% and 30.3% in those with low or high TKa, respectively (p = 0.022). The median PFS was 19.9 and 12.6 months in patients with low or high TKa, respectively (hazard ratio (HR) 1.83 (95% CI, 1.08–3.08), p = 0.024). The median OS was >60 months and 18.5 months in patients with low or high TKa, respectively (HR: 2.25 (95% CI, 1.25–4.05), p = 0.011. Conclusions. High pretreatment plasma TKa levels were significantly associated with worse baseline characteristics and poor response and survival in ICI-treated melanoma patients. TKa is hence a novel and interesting plasma biomarker in melanoma and should be further studied to define its role as a prognostic and predictive marker in this disease. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Ekstrand, Vilhelm, et al.
(author)
-
Influence of electrical and thermal properties on RF ablation of breast cancer: is the tumour preferentially heated?
- 2005
-
In: Biomedical engineering online. - 1475-925X. ; 4, s. 41-41
-
Journal article (peer-reviewed)abstract
- Background: Techniques based on radio frequency (RF) energy have many applications in medicine, in particular tumour ablation. Today, mammography screening detects many breast cancers at an early stage, facilitating treatment by minimally invasive techniques such as radio frequency ablation (RFA). The breast cancer is mostly surrounded by fat, which during RFA-treatment could result in preferential heating of the tumour due to the substantial differences in electrical parameters. The object of this study was to investigate if this preferential heating existed during experimental in vitro protocols and during computer simulations. Methods: Excised breast material from four patients with morphologically diagnosed breast cancers were treated with our newly developed RFA equipment. Subsequently, two finite element method (FEM) models were developed; one with only fat and one with fat and an incorporated breast cancer of varying size. The FEM models were solved using temperature dependent electrical conductivity versus constant conductivity, and transient versus steady-state analyses. Results: Our experimental study performed on excised breast tissue showed a preferential heating of the tumour, even if associated with long tumour strands. The fat between these tumour strands was surprisingly unaffected. Furthermore, the computer simulations demonstrated that the difference in electrical and thermal parameters between fat and tumour tissue can cause preferential heating of the tumour. The specific absorption rate (SAR) distribution changed significantly when a tumour was present in fatty tissue. The degree of preferential heating depended on tissue properties, tumour shape, and placement relative to the electrode. Temperature dependent electrical conductivity increased the thermal lesion volume, but did not change the preferential heating. Transient solutions decreased the thermal lesion volume but increased the preferential heating of the tumour. Conclusions: Both the computer model and the in vitro study confirmed that preferential heating of the tumour during RFA exists in breast tissue. However, the observed preferential heating in the in vitro studies were more pronounced, indicating that additional effects other than the difference in tissue parameters might be involved. The existing septa layers between the cancer tissue and the fatty tissue could have an additional electrical or thermal insulating effect, explaining the discrepancy between the in vitro study and the computer model.
|
|
| 10. |
- Hatschek, T, et al.
(author)
-
Individually tailored treatment with epirubicin and paclitaxel with or without capecitabine as first-line chemotherapy in metastatic breast cancer: a randomized multicenter trial
- 2012
-
In: Breast Cancer Research and Treatment. - New York, USA : Springer Verlag (Germany). - 0167-6806 .- 1573-7217. ; 131:3, s. 939-947
-
Journal article (peer-reviewed)abstract
- Anthracyclines and taxanes are active cytotoxic drugs in the treatment of early metastatic breast cancer. It is yet unclear whether addition of capecitabine to the combination of these drugs improves the treatment outcome. Patients with advanced breast cancer were randomized to first-line chemotherapy with a combination of epirubicin (Farmorubicin(A (R))) and paclitaxel (Taxol(A (R))) alone (ET) or in combination with capecitabine (Xeloda(A (R)), TEX). Starting doses for ET were epirubicin 75 mg/m(2) plus paclitaxel 175 mg/m(2), and for TEX epirubicin 75 mg/m(2), paclitaxel 155 mg/m(2), and capecitabine 825 mg/m(2) BID for 14 days. Subsequently, doses were tailored related to side effects. Primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), time to treatment failure (TTF), objective response (OR), safety and quality of life (QoL). 287 patients were randomized, 143 to ET and 144 to TEX. Median PFS was 10.8 months for patients treated with ET, and 12.4 months for those treated with TEX (HR 0.84, 95% CI 0.65-1.07, P = 0.16); median OS was 26.0 months for women in the ET versus 29.7 months in the TEX arm (HR 0.84, 95% CI 0.63-1.11, P = 0.22). OR was achieved in 44.8% (ET) and 54.2% (TEX), respectively (chi(2) 3.66, P = 0.16). TTF was significantly longer for patients treated with TEX, 6.0 months, versus 5.2 months following ET (HR 0.73, 95% CI 0.58-0.93, P = 0.009). Severe hematological side effects related to epirubicin and paclitaxel were evenly distributed between the treatment arms, mucositis, diarrhea, and Hand-Foot syndrome were significantly more frequent in the TEX arm. Toxicity-adjusted treatment with ET and TEX showed similar efficacy in terms of PFS, OS, and OR. In this trial with limited power, the addition of capecitabine to epirubicin and paclitaxel as first-line treatment did not translate into clinically relevant improvement of the outcome.
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Lekander, M, et al.
(author)
-
Anticipatory immune changes in women treated with chemotherapy for ovarian-cancer
- 1995
-
In: INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE. - : LAWRENCE ERLBAUM ASSOC INC. - 1070-5503. ; 2:1, s. 1-12
-
Journal article (peer-reviewed)abstract
- Immune parameters were assessed in 22 women before chemotherapy for ovarian cancer and compared with assessment made at home 2 days earlier. In the hospital, as compared to home measures, patients had a lower percentage of lymphocytes and monocytes and a
|
|
| 15. |
|
|
| 16. |
- Lekander, M, et al.
(author)
-
Immune effects of relaxation during chemotherapy for ovarian cancer
- 1997
-
In: PSYCHOTHERAPY AND PSYCHOSOMATICS. - : KARGER. - 0033-3190. ; 66:4, s. 185-191
-
Journal article (peer-reviewed)abstract
- Background: Psychological interventions, such as relaxation training, have been applied to strengthen resistance to disease. There is evidence that relaxation can modify immune parameters in healthy populations and in chemotherapy naive cancer patients.
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
- Matikas, A., et al.
(author)
-
Prognostic role of serum thymidine kinase 1 kinetics during neoadjuvant chemotherapy for early breast cancer
- 2021
-
In: ESMO open. - : Elsevier BV. - 2059-7029. ; 6:2
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Emerging data support the use of thymidine kinase 1 (TK1) activity as a prognostic marker and for monitoring of response in breast cancer (BC). The long-term prognostic value of TK1 kinetics during neoadjuvant chemotherapy is unclear, which this study aimed to elucidate. METHODS: Material from patients enrolled to the single-arm prospective PROMIX trial of neoadjuvant epirubicin, docetaxel and bevacizumab for early BC was used. Ki67 in baseline biopsies was assessed both centrally and by automated digital imaging analysis. TK1 activity was measured from blood samples obtained at baseline and following two cycles of chemotherapy. The associations of TK1 and its kinetics as well as Ki67 with event-free survival and overall survival (OS) were evaluated using multivariable Cox regression models. RESULTS: Central Ki67 counting had excellent correlation with the results of digital image analysis (r= 0.814), but not with the diagnostic samples (r= 0.234), while it was independently prognostic for worse OS [adjusted hazard ratio (HRadj) = 2.72, 95% confidence interval (CI) 1.19-6.21, P= 0.02]. Greater increase in TK1 activity after two cycles of chemotherapy resulted in improved event-free survival (HRadj= 0.50, 95% CI 0.26-0.97, P= 0.04) and OS (HRadj= 0.46, 95% CI 0.95, P= 0.04). There was significant interaction between the prognostic value of TK1 kinetics and Ki67 (pinteraction 0.04). CONCLUSION: Serial measurement of serum TK1 activity during neoadjuvant chemotherapy provides long-term prognostic information in BC patients. The ease of obtaining serial samples for TK1 assessment motivates further evaluation in larger studies. Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
|
|
| 30. |
|
|
| 31. |
|
|
| 32. |
|
|
| 33. |
|
|
| 34. |
|
|
| 35. |
- Xu, N, et al.
(author)
-
Transplantation of Human Neural Precursor Cells Reverses Syrinx Growth in a Rat Model of Post-Traumatic Syringomyelia
- 2021
-
In: Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics. - : Springer Science and Business Media LLC. - 1878-7479. ; 18:2, s. 1257-1272
-
Journal article (peer-reviewed)abstract
- Posttraumatic syringomyelia (PTS) is a serious condition of progressive expansion of spinal cord cysts, affecting patients with spinal cord injury years after injury. To evaluate neural cell therapy to prevent cyst expansion and potentially replace lost neurons, we developed a rat model of PTS. We combined contusive trauma with subarachnoid injections of blood, causing tethering of the spinal cord to the surrounding vertebrae, resulting in chronically expanding cysts. The cysts were usually located rostral to the injury, extracanalicular, lined by astrocytes. T2*-weighted magnetic resonance imaging (MRI) showed hyperintense fluid-filled cysts but also hypointense signals from debris and iron-laden macrophages/microglia. Two types of human neural stem/progenitor cells—fetal neural precursor cells (hNPCs) and neuroepithelial-like stem cells (hNESCs) derived from induced pluripotent stem cells—were transplanted to PTS cysts. Cells transplanted into cysts 10 weeks after injury survived at least 10 weeks, migrated into the surrounding parenchyma, but did not differentiate during this period. The cysts were partially obliterated by the cells, and cyst walls often merged with thin layers of cells in between. Cyst volume measurements with MRI showed that the volumes continued to expand in sham-transplanted rats by 102%, while the cyst expansion was effectively prevented by hNPCs and hNESCs transplantation, reducing the cyst volumes by 18.8% and 46.8%, respectively. The volume reductions far exceeded the volume of the added human cells. Thus, in an animal model closely mimicking the clinical situation, we provide proof-of-principle that transplantation of human neural stem/progenitor cells can be used as treatment for PTS.
|
|
