| 1. |
- Bill-Axelson, Anna, et al.
(author)
-
Radical prostatectomy versus watchful waiting in localized prostate cancer : the Scandinavian prostate cancer group-4 randomized trial
- 2008
-
In: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 100:16, s. 1144-1154
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The benefit of radical prostatectomy in patients with early prostate cancer has been assessed in only one randomized trial. In 2005, we reported that radical prostatectomy improved prostate cancer survival compared with watchful waiting after a median of 8.2 years of follow-up. We now report results after 3 more years of follow-up.METHODS: From October 1, 1989, through February 28, 1999, 695 men with clinically localized prostate cancer were randomly assigned to radical prostatectomy (n = 347) or watchful waiting (n = 348). Follow-up was complete through December 31, 2006, with histopathologic review and blinded evaluation of causes of death. Relative risks (RRs) were estimated using the Cox proportional hazards model. Statistical tests were two-sided.RESULTS: During a median of 10.8 years of follow-up (range = 3 weeks to 17.2 years), 137 men in the surgery group and 156 in the watchful waiting group died (P = .09). For 47 of the 347 men (13.5%) who were randomly assigned to surgery and 68 of the 348 men (19.5%) who were not, death was due to prostate cancer. The difference in cumulative incidence of death due to prostate cancer remained stable after about 10 years of follow-up. At 12 years, 12.5% of the surgery group and 17.9% of the watchful waiting group had died of prostate cancer (difference = 5.4%, 95% confidence interval [CI] = 0.2 to 11.1%), for a relative risk of 0.65 (95% CI = 0.45 to 0.94; P = .03). The difference in cumulative incidence of distant metastases did not increase beyond 10 years of follow-up. At 12 years, 19.3% of men in the surgery group and 26% of men in the watchful waiting group had been diagnosed with distant metastases (difference = 6.7%, 95% CI = 0.2 to 13.2%), for a relative risk of 0.65 (95% CI = 0.47 to 0.88; P = .006). Among men who underwent radical prostatectomy, those with extracapsular tumor growth had 14 times the risk of prostate cancer death as those without it (RR = 14.2, 95% CI = 3.3 to 61.8; P < .001).CONCLUSION: Radical prostatectomy reduces prostate cancer mortality and risk of metastases with little or no further increase in benefit 10 or more years after surgery.
|
|
| 2. |
- Alers, Margret, et al.
(author)
-
Gendered career considerations consolidate from the start of medical education
- 2014
-
In: International Journal of Medical Education. - : International Journal of Medical Education. - 2042-6372. ; 5, s. 178-184
-
Journal article (peer-reviewed)abstract
- Objectives: To explore changes in specialty preferences and work-related topics during the theoretical phase of Dutch medical education and the role of gender.Methods: A cohort of medical students at Radboudumc, the Netherlands, was surveyed at start (N=612, 69.1% female) and after three years (N=519, 69.2% female), on specialty preferences, full-time or part-time work, motivational factors, and work-life issues. Chi square tests were performed to analyze gender-differences, and logistic regression to explore the influence of gender on considerations.Results: A total of 214 female and 78 male students completed both surveys. After three years, the male students remained highly interested in surgery, but the female students increasingly preferred gynecology. These initial preferences were predictive. Four out of five male students versus three out of five female students continued to show a full-time preference. Women increasingly preferred part-time work. After three years, the combination of work, care, and patient contact motivated female students more, whereas salary remained more important to male students. Female students indicated that their future careers would influence their family life; male students assumed having a family would only affect their partners' careers.Conclusions: Against an international background of the feminization of medicine, our study shows that career considerations are reinforced early in medical studies. Women prefer to work fewer hours and anticipate care tasks more often. Students' preferences reflect Dutch cultural norms about working men and women. Therefore, guidance in choice-making much earlier in medical education can create opportunities.
|
|
| 3. |
- Alers, Margret, et al.
(author)
-
Speciality preferences in Dutch medical students influenced by their anticipation on family responsibilities
- 2014
-
In: Perspectives on Medical Eduction. - : Springer. - 2212-277X. ; 3:6, s. 443-454
-
Journal article (peer-reviewed)abstract
- Physician gender is associated with differences in the male-to-female ratio between specialities and with preferred working hours. We explored how graduating students’ sex or full-time or part-time preference influences their speciality choice, taking work-life issues into account. Graduating medical students at Radboud University Medical Centre, the Netherlands participated in a survey (2008–2012) on career considerations. Logistic regression tested the influence of sex or working hour preference on speciality choice and whether work-life issues mediate. Of the responding students (N = 1,050, response rate 83, 73.3 % women), men preferred full-time work, whereas women equally opted for part time. More men chose surgery, more women family medicine. A full-time preference was associated with a preference for surgery, internal medicine and neurology, a part-time preference with psychiatry and family medicine. Both male and female students anticipated that foremost the career of women will be negatively influenced by family life. A full-time preference was associated with an expectation of equality in career opportunities or with a less ambitious partner whose career would affect family life. This increased the likelihood of a choice for surgery and reduced the preference for family medicine among female students. Gender specifically plays an important role in female graduates’ speciality choice making, through considerations on career prospects and family responsibilities.
|
|
| 4. |
- Andjelkov, Nenad, et al.
(author)
-
No outgrowth of chondrocytes from non-digested particulated articular cartilage embedded in commercially available fibrin matrix : an in vitro study
- 2016
-
In: Journal of Orthopaedic Surgery and Research. - : Springer Science and Business Media LLC. - 1749-799X. ; 11
-
Journal article (peer-reviewed)abstract
- Background: Commercially available fibrin is routinely being used as both a matrix in certain cartilage repair techniques and a method for scaffold fixation. Chondrocytes from non-digested particulated cartilage fragments are proposed as a possible source for new cartilage tissue formation in some operative techniques. The goal of this study was to test that chondrocytes from particulated articular cartilage embedded in fibrin have an active role in the process of cartilage repair, as well as if commercially available fibrin should be used as a suitable matrix. Methods: Articular cartilage was obtained from patients undergoing total knee replacement surgery. The biopsies were particulated in small, 1-2-mm(3) pieces and embedded in fibrin. Two groups were compared in our study, particulated articular cartilage with and without collagenase treatment. The specimens were analyzed by optical microscopy after 2-5 weeks of cultivation in a special construct embedded in a cell culture medium containing particulated cartilage embedded in fibrin in the upper phase and cancellous bone in the lower phase under the perforated nylon membrane. Results: None of the biopsies taken from four different patients showed the outgrowth of chondrocytes or bone marrow-originated cells into the fibrin matrix in our experimental model. Conclusions: It has been shown in our experimental model in vitro little to support the theory that articular chondrocytes from particulated articular cartilage embedded in fibrin have an active role in cartilage repair in its early stage.
|
|
| 5. |
- Barbaro, Michela, et al.
(author)
-
Complete androgen insensitivity without Wolffian duct development : the AR-A form of the androgen receptor is not sufficient for male genital development
- 2007
-
In: Clinical Endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 66:6, s. 822-826
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The androgen receptor (AR) is essential for the differentiation of male external and internal genitalia. It is normally present in two forms, a full-length form B and an N-terminal truncated form A with still unknown function. Mutations in the AR gene cause androgen insensitivity syndrome (AIS), which is divided into subgroups according to the degree of undermasculinization. Patients with completely female external genitalia are classified as complete AIS (CAIS). However, a recent study has shown that some CAIS patients have signs of internal male genital differentiation due to missense mutations that show some degree of residual function. OBJECTIVE: We aimed to study the expression of the different forms of the AR in two CAIS patients in relation to the development of male internal genital structures. One patient had a mutation (L7fsX33) that affects only the full-length AR-B form of the AR, whereas the other had a nonsense mutation (Q733X) affecting both isoforms. MEASUREMENTS AND RESULTS: We thoroughly analysed internal genitalia at surgery and by histological examination. No signs of Wolffian duct (WD) development were present in any of the patients. Western blotting of proteins from gonadal and genital skin fibroblasts was performed with AR antibodies directed against different AR epitopes. The N-terminally truncated A form was expressed in normal amounts in the patient with the L7fsX33 mutation while no AR was detected in the other patient. CONCLUSION: The presence of the AR-A form does not seem to be sufficient for WD maintenance and differentiation.
|
|
| 6. |
- Brunnström, Åsa, et al.
(author)
-
Biosynthesis of 14,15-Hepoxilins in Human L1236 Hodgkin Lymphoma Cells and Eosinophils
- 2011
-
In: Lipids. - : Wiley. - 0024-4201 .- 1558-9307. ; 46:1, s. 69-79
-
Journal article (peer-reviewed)abstract
- Hepoxilins are epoxy alcohols synthesized through the 12-lipoxygenase (12-LO) pathway in animal cells. The epidermis is the principal source of hepoxilins in humans. Here we report on the formation of novel hepoxilin regioisomers formed by the 15-LO pathway in human cells. The Hodgkin lymphoma cell line L1236 possesses high 15-lipoxygenase-1 (15-LO-1) activity and incubation of L1236 cells with arachidonic acid led to the formation of 11(S)-hydroxy-14(S),15(S)-epoxy 5(Z),8(Z),12(E) eicosatrienoic acid (14,15-HxA(3) 11(S)) and 13(R)-hydroxy-14(S),15(S)-epoxy 5(Z),8(Z),11(Z) eicosatrienoic acid (14,15-HxB(3) 13 (R)). In addition, two hitherto unidentified products were detected and these products were collected and analyzed by positive ion electrospray tandem mass spectrometry. These metabolites were identified as 11(S),15(S)-dihydroxy-14(R)-glutathionyl-5(Z),8(Z),12(E)-eicosatrienoic acid (14,15-HxA(3)-C) and 11(S),15(S)-dihydroxy-14(R)-cysteinyl-glycyl-5(Z),8(Z),12(E)-eicosatrien oic acid (14,15-HxA(3)-D). Incubation of L1236 cells with synthetic 14,15-HxA(3) 11(S) also led to the formation of 14,15-HxA(3)-C and 14,15-HxA(3)-D. Several soluble glutathione transferases, in particular GST M1-1 and GST P1-1, were found to catalyze the conversion of 14,15-HxA(3) to 14,15-HxA(3)-C. L1236 cells produced approximately twice as much eoxins as cysteinyl-containing hepoxilins upon stimulation with arachidonic acid. Human eosinophils, nasal polyps and dendritic cells selectively formed 14,15-HxA(3) 11(S) and 14,15-HxB(3) 13(R) stereoisomers, but not cysteinyl-containing hepoxilins, after stimulation with arachidonic acid. Furthermore, purified recombinant 15-LO-1 alone catalyzed the conversion of arachidonic acid to 14,15-HxA(3) 11(S) and 14,15-HxB(3) 13(R), showing that human 15-LO-1 possesses intrinsic 14,15-hepoxilin synthase activity.
|
|
| 7. |
|
|
| 8. |
- Forsberg, Ole, 1979-, et al.
(author)
-
Identification of prostate infiltrating lymphocytes and activation of prostate antigen-specific T cells isolated from prostate cancer patients
-
Other publication (other academic/artistic)abstract
- Although prostate antigen-specific CD8+ T lymphocytes have been found both in peripheral blood and in tumor area of prostate cancer patients there has not yet been any adequate adoptive T lymphocyte transfer trial for prostate cancer patients. Methods for efficient generation of large number of prostate antigen-specific T cells are still lacking. In the present study we isolate and expand prostate infiltrating lymphocytes (PILs) from resected prostates by fine needle aspiration of patients with localized prostate cancer. By using HLA-A*0201-restricted tetramers, specific for the prostate tumor-associated antigen epitopes TARP(P5L)4-13, STEAP262-270 and PSA53-61, we were able to identify prostate antigen-specific CD8+ PILs in 5 out of 5 patients. Most frequent were STEAP262-270-specific T cells (5/5). Furthermore, by using fast-matured dendritic cells (DCs) transduced with an adenoviral vector encoding the STEAP antigen we were able to generate CD8+ T cells from peripheral blood of prostate cancer patients, for three HLA-A*0201-restricted STEAP epitopes simultaneously by one stimulation only. If combined, an effective protocol for generation of prostate antigen-specific T cells may be developed.
|
|
| 9. |
|
|
| 10. |
- Johnsson, Anna-Karin, et al.
(author)
-
COX-1 dependent biosynthesis of 15-hydroxyeicosatetraenoic acid in human mast cells
- 2021
-
In: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids. - : Elsevier. - 1388-1981 .- 1879-2618. ; 1866:5
-
Journal article (peer-reviewed)abstract
- 15-hydroxyeicosatetraenoic acid (15-HETE) is an arachidonic acid derived lipid mediator which can originate both from 15-lipoxygenase (15-LOX) activity and cyclooxygenase (COX) activity. The enzymatic source determines the enantiomeric profile of the 15-HETE formed. 15-HETE is the most abundant arachidonic acid metabolite in the human lung and has been suggested to influence the pathophysiology of asthma. Mast cells are central effectors in asthma, but there are contradictory reports on whether 15-HETE originates from 15-LOX or COX in human mast cells. This prompted the current study where the pathway of 15-HETE biosynthesis was examined in three human mast cell models; the cell line LAD2, cord blood derived mast cells (CBMC) and tissue isolated human lung mast cells (HLMC). Levels and enantiomeric profiles of 15-HETE and levels of the downstream metabolite 15-KETE, were analyzed by UPLC-MS/MS after stimulation with anti-IgE or calcium ionophore A23187 in the presence and absence of inhibitors of COX isoenzymes. We found that 15-HETE was produced by COX-1 in human mast cells under these experimental conditions. Unexpectedly, chiral analysis showed that the 15(R) isomer was predominant and gradually accumulated, whereas the 15(S) isomer was metabolized by the 15hydroxyprostaglandin dehydrogenase. We conclude that during physiological conditions, i.e., without addition of exogenous arachidonic acid, both enantiomers of 15-HETE are produced by COX-1 in human mast cells but that the 15(S) isomer is selectively depleted by undergoing further metabolism. The study highlights that 15-HETE cannot be used as an indicator of 15-LOX activity for cellular studies, unless chirality and sensitivity to pharmacologic inhibition is determined.
|
|
