| 1. |
- Aschim, Elin L, et al.
(författare)
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The RsaI polymorphism in the ER{beta} gene is associated with male infertility.
- 2005
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 90:Jul 5, s. 5343-5348
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Tidskriftsartikel (refereegranskat)abstract
- Context: Hypospadias, cryptorchidism, testicular cancer, and low semen quality have been proposed as being parts of the testicular dysgenesis syndrome (TDS) hypothetically due to changes in the androgen- estrogen balance in utero. Estrogens and estrogen receptors (ERs) play a role in regulating testicular function. ER beta contains two silent polymorphisms, RsaI (G1082A) and AluI (G1730A). Objective: We investigated the significance of these polymorphisms in the etiology of disorders being part of TDS. Setting: The patients were recruited consecutively through university hospital clinics. Participants: Four groups of Caucasian patients were included: 106 men from infertile couples with a sperm concentration less than 5 x 106 spermatozoa/ ml, 86 testicular cancer patients, 51 boys with hypospadias, and 23 cases with cryptorchidism. Military conscripts (n = 186) with sperm concentration higher than 5 x 10(6) spermatozoa/ ml served as controls. Main Outcome Measures: ER beta polymorphisms RsaI and AluI were determined by allele-specific PCR. In addition, reproductive hormone analyses were performed in controls and infertile men. Results: Compared with the controls, the frequency of the heterozygous RsaI AG-genotype was three times higher in infertile men (13.2 vs. 4.3%; P = 0.01). The heterozygous RsaI AG-genotype was associated with an approximately 20% reduction in LH concentration, compared with the wild-type RsaI GG genotype in both controls and infertile men. Subjects with testicular cancer, hypospadias, or cryptorchidism did not differ from controls regarding the frequency of any of the polymorphisms. Conclusions: Polymorphisms in ER beta may have modulating effects on human spermatogenesis. The phenotype of TDS seems to be, at least partly, determined by the genotype.
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| 2. |
- Cwikiel, Magdalena, et al.
(författare)
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Changes of blood viscosity in pateints treated with 5-fluorouracil : A link to cardiotoxicity?
- 1995
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Ingår i: Acta Oncologica. - Norway. - 0284-186X .- 1651-226X. ; 34:1, s. 83-85
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Cardiotoxicity is a serious but relatively unknown side-effect of treatment with 5-fluorouracil (5-FU). The underlying mechanism of 5-FU cardiotoxicity has not been defined. The aim of the present study was to determine whether hemorheological factors might in part explain 5-FU cardiotoxicity. Changes of blood and plasma viscosity, fibrinogen and hematocrit were studied in 11 patients treated by 5-FU. The study showed a decrease in blood and plasma viscosity during treatment with 5-FU, probably caused by a decrease of plasma fibrinogen. Reversible cardiotoxic effects were demonstrated in four patients.
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| 3. |
- Cwikiel, Magdalena
(författare)
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Pathophysiology of 5-fluorouracil induced cardiotoxicity : a clinical and experimental study
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis concerns the pathophysiology of 5-fluorouracil (5-FU) induced cardiotoxicity. The aim of the clinical studies was to determine whether hemorheological factors might explain 5-FU cardiotoxicity (I) and if the syndrome was associated with free radical (FR) generation and lipid peroxidation (II). Changes in blood and plasma viscosity, fibrinogen, hematocrit, and thiobarbituric acid-reactive substances (TBARS) were studied in patients with esophageal or head and neck carcinoma during treatment with 5-FU. The study showed a decrease in blood and plasma viscosity, probably caused by a decrease in fibrinogen. Study of TBARS did not support the hypothesis that FRs could be involved in the cardiotoxicity of 5-FU. In the experimental studies in rabbits (III,IV) we examined the early and late, local and systemic effect of 5-FU on endothelium, using scanning and transmission electron microscopic evaluation of small arteries, after in vivo treatment with 5-FU. Perfusion fixation was used. The following parameters were evaluated: vessel wall and endothelial cell (EC) contraction, EC edema, cytolysis, denuded areas, platelet accumulation, fibrin formation. The studies showed severe damage to ECs with accompanying thrombus formation, supporting the hypothesis that the thrombogenic effect of 5-FU, secondary to its direct cytotoxic effect on the endothelium is the pathophysiological mechanism of 5-FU cardiotoxicity. The influence of 5-FU on endothelial cell lines in a cell culture model was studied with regard to DNA synthesis, cell death and release of prostacyclin (V). Methotrexate (MTX), an antimetabolite without cardiotoxic properties, was tested in the same way. (3H)thymidine incorporation, total cellular protein, loss of (3H)thymidine from prelabelled cells, 6-keto-prostaglandin F1* were measured. DNA synthesis decreased significantly and the release of prostacyclin by ECs increased significantly when incubated with 5-FU; this effect was not seen for MTX. The study indicate specific susceptibility of benign EC for 5-FU.
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| 4. |
- Eberhard, Jakob, et al.
(författare)
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Impact of therapy and androgen receptor polymorphism on sperm concentration in men treated for testicular germ cell cancer: a longitudinal study.
- 2004
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 19:6, s. 1418-1425
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Tidskriftsartikel (refereegranskat)abstract
- Abstract in Undetermined BACKGROUND: Testicular cancer (TC) patients have a high survival rate, and the question of post-therapy recovery of sperm production and its dependence on genetic predisposition is of major interest. METHODS: Ejaculates were obtained from 112 TC patients at one or more of the following time points: post-orchidectomy, or 6, 12, 24, 36 and 60 months post-therapy. The lengths of the androgen receptor (AR) function modulating CAG and GGN repeats in leukocyte DNA were also analysed. RESULTS: No significant decrease in sperm concentration was seen in men who received 1-2 cycles of adjuvant chemotherapy (ACT). Radiotherapy (RT) or more than two cycles of chemotherapy (HCT) caused an initial decline in sperm concentration, which returned to pre-treatment levels 2-5 years after therapy. In the HCT group, sperm concentration 12-24 months post-treatment (T(12-24)) was inversely correlated with CAG length (rho = -0.72, P = 0.03). The type of treatment, but not the concentration at T(0), was an independent predictor of sperm concentration at T(6) (P < 0.0005) and T(12-24) (P = 0.004). CONCLUSION: ACT did not induce a significant decline in sperm concentration. After HCT and RT, a significant reduction of sperm concentration was observed, recovering to pre-treatment levels 2-5 years post-treatment. In HCT-treated patients, the AR CAG length influenced the recovery of spermatogenesis.
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| 5. |
- Eberhard, Jakob, et al.
(författare)
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Risk factors for post-treatment hypogonadism in testicular cancer patients.
- 2008
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 158:4, s. 561-570
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Testicular germ-cell cancer (TGCC) patients are at risk of developing hypogonadism but no risk factors have yet been defined. METHODS: Blood was collected from 143 TGCC patients (after orchidectomy, prior to further therapy (T0) and 6, 12, 24, 36 and 60 months (T6, T12, T24, T36 and T60) after therapy). Biological hypogonadism (BH) was defined as: serum testosterone below 10 nmol/l and/or LH >10 IU/l; odds ratios (ORs) for BH with BH at T0, age, stage of disease, testicular characteristics, and androgen receptor polymorphism as predictors were calculated as well as the OR for developing BH post-treatment (one to two cycles of adjuvant chemotherapy (ACT) versus three to four cycles of higher dose chemotherapy (HCT) versus adjuvant radiotherapy (RT)). RESULTS: HCT increased the OR for BH at T6 (OR 22, 95% confidence interval (CI) 4.4-118) and T12 (OR 5.8, 95% CI 1.5-22). RT increased the OR at T6 (OR 10, 95% CI 2.1-47) and at T12 (OR 3.9, 95% CI 1.1-14). Microlithiasis predicted BH at T0 (OR 11, 95% CI 1.2-112), T12 (OR 3.9, 95% CI 1.1-13), T24 (OR 3.0, 95% CI 1.0-8.8), T36 (OR 5.4, 95% CI 1.7-17) and T60 (OR 4.4, 95% CI 1.2-16). BH at T0 was a risk for BH at T6 (OR 53, 95% CI 19-145), T12 (OR 125, 95% CI 37-430), T24 (OR 88, 95% CI 26-300) and T36 (OR 121, 95% CI 32-460). CONCLUSIONS: It is clinically relevant that BH at T0 and testicular microlithiasis were predictive factors for post-treatment BH. HCT and RT gave temporary BH.
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| 6. |
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| 7. |
- Gustavsson, Anita, et al.
(författare)
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No serious late cardiac effects after adjuvant radiotherapy following mastectomy in premenopausal women with early breast cancer
- 1999
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - 0360-3016. ; 43:4, s. 745-754
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To assess cardiac mortality, coronary artery disease, myocardial dysfunction, and valvular heart disease in women younger than 65 years of age, at least 10 years after adjuvant radiotherapy following mastectomy in early breast cancer. METHODS AND MATERIALS: Ninety women (45-64 years old) with Stage II breast cancer without relapse, included in the South Sweden Breast Cancer Trial (premenopausal arm), with or without adjuvant postoperative radiotherapy +/- cyclophosphamide were examined with myocardial scintigraphy and echocardiography/Doppler, 10-17 years after radiotherapy. Thirty-four patients had been irradiated for left-sided tumors, 33 for right-sided tumors, and 23 patients had not been treated with radiotherapy. The radiotherapy (conventional roentgen, electron beams, and high-energy photon beams combined, in each patient) included the chest wall and the regional lymph nodes, with a specified target dose of 38-48 Gy, administered in daily fractions of 1.9-2.4 Gy, 5 days/week. RESULTS: No cardiac deaths were found among the original 275 patients randomized to adjuvant therapy. In the 90 patients examined, abnormal findings were recorded for ECG (14 patients), exercise test (5 patients), myocardial scintigraphy (6 patients), thickening of valve cusps (14 patients), and mild valvular regurgitation (20 patients). All patients had normal systolic function. Diastolic dysfunction was observed in 6 patients (abnormal relaxation in 4 patients and restrictive filling abnormality in 2 patients). Although no significant differences were found between the 3 study groups, there was a tendency to more abnormal findings after radiotherapy. CONCLUSION: Women younger than 50 years of age at the time of adjuvant radiotherapy following mastectomy in early breast cancer, had no serious cardiac sequelae 13 years (median) later, despite partly old-fashioned radiation techniques.
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| 8. |
- Johansson Kollberg, Petter, et al.
(författare)
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[18F]Fluorodeoxyglucose-positron emission tomography/computed tomography response evaluation can predict histological response at surgery after induction chemotherapy for oligometastatic bladder cancer
- 2017
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 51:4, s. 308-313
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Patients with limited metastatic and locally advanced bladder cancer have a poor prognosis, and no definite treatment recommendations exist. However, long-term survival is possible for selected patients if surgery is combined with multiple courses of chemotherapy (i.e. induction chemotherapy). Patients with tumours that are insensitive to chemotherapy probably have little to gain from subsequent extensive surgery. The aim of this study was to evaluate sequential FDG-PET/CT examinations as an indicator of chemotherapy response. Materials and methods: Between 2007 and 2015, 50 patients with oligometastatic invasive bladder cancer selected for induction chemotherapy underwent two FDG-PET/CT examinations: the first before the start of chemotherapy and the second after three courses of cisplatinum-based combination chemotherapy. Responders were given up to six courses of chemotherapy. FDG-PET/CT response was correlated with histological response in excised lymph-node metastases. Results: Three patients showed progression to incurable disease during chemotherapy and another two patients did not undergo surgery, for medical reasons. Lymphadenectomy was performed in the remaining 45 patients, of whom 43 had lymph-node metastasis. FDG-PET/CT prediction of the histological nodal chemotherapy response was correct in 37 (86%) of those 43. The second FDG-PET/CT examination identified four out of nine non-responders. For response, the sensitivity, specificity, and positive and negative predictive values for FDG-PET/CT accuracy were 37 out of 37 (100%), one out of six (17%), 37 out of 42 (88%) and one out of one (100%), respectively. Conclusions: Repeated FDG-PET/CT seems to predict histological response. However, with the histological response criteria used in this study, five non-responders were not identified by the second FDG-PET/CT investigation.
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| 9. |
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| 10. |
- Kinhult, Sara, et al.
(författare)
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Endothelial damage after treatment with low-molecular weight heparins - a morphological study
- 2003
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Ingår i: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1651-2006 .- 1401-7431. ; 37:1, s. 30-33
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Tidskriftsartikel (refereegranskat)abstract
- Objective-Recent studies failed to show long-term benefit with low-molecular weight heparins (LMWH) in unstable coronary heart disease. A previous study of vascular effects of the cytostatic agent 5-fluorouracil (5-FU) showed that dalteparin prevented thrombosis induced by 5-FU but endothelial damage was not ameliorated and was present also in animals treated with dalteparin only. This study investigates the influence of LMWH currently in clinical use on arterial endothelium in vivo. Design-Eighty rabbits in four groups were treated with dalteparin, enoxaparin, tinzaparin and saline, respectively. Arterial endothelium was examined after 3, 14, 30 and 60 days with scanning electron microscopy. Results-All three groups treated with LMWH showed moderate damage to the endothelium, with contracted vessel wall and endothelial cells, cell membrane damage, denudation of subendothelium and adhering platelets. Contrarily, the control group exhibited a normal endothelium. Conclusion-Morphologic examination of arterial endothelium shows that all investigated LMWH exert a moderate toxic effect on endothelial cells. The clinical impact of these observations, e. g. concerning effect of long-term LMWH treatment, needs to be further elucidated.
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