| 1. |
- Hall, Per, et al.
(författare)
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Hormone-replacement therapy influences gene expression profiles and is associated with breast-cancer prognosis : a cohort study
- 2006
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Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 4, s. 16-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Postmenopausal hormone-replacement therapy (HRT) increases breast-cancer risk. The influence of HRT on the biology of the primary tumor, however, is not well understood. Methods: We obtained breast-cancer gene expression profiles using Affymetrix human genome U133A arrays. We examined the relationship between HRT-regulated gene profiles, tumor characteristics, and recurrence-free survival in 72 postmenopausal women. Results: HRT use in patients with estrogen receptor ( ER) protein positive tumors (n = 72) was associated with an altered regulation of 276 genes. Expression profiles based on these genes clustered ER-positive tumors into two molecular subclasses, one of which was associated with HRT use and had significantly better recurrence free survival despite lower ER levels. A comparison with external data suggested that gene regulation in tumors associated with HRT was negatively correlated with gene regulation induced by short-term estrogen exposure, but positively correlated with the effect of tamoxifen. Conclusion: Our findings suggest that post-menopausal HRT use is associated with a distinct gene expression profile related to better recurrence-free survival and lower ER protein levels. Tentatively, HRT-associated gene expression in tumors resembles the effect of tamoxifen exposure on MCF-7 cells.
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| 2. |
- Hardell, Lennart, et al.
(författare)
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High concentrations of organochlorines in a patient with kidney cancer and anorexia-cachexia syndrome
- 2006
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Ingår i: Medicinal chemistry (Shāriqah (United Arab Emirates)). - : Bentham Science Publishers Ltd.. - 1573-4064. ; 2:6, s. 607-610
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To determine persistent organic pollutants in adipose tissue in a patient with kidney cancer. METHODS: Adipose tissue was sampled from the abdominal wall during autopsy of a 75-year old man who had died from a kidney cancer. The concentrations of polychlorinated biphenyls (PCBs), p,p'-dichlorodiphenyltrichloroethane (DDE), hexachlorobenzene (HCB), chlordanes and tetrabromodiphenyl ether (TeBDE) were determined on lipid basis. For comparison results from 29 male population based subjects aged 70-80 years were used. RESULTS: All concentrations except for TeBDE were very high in the patient; sum of PCBs 18 808 ng/g fat (median for controls 997), DDE 14 183 (median for controls 751), HCB 424 (median for controls 46), and sum of chlordanes 2 389 (median for controls 62). The patient lost weight from 80 kg to 48 kg when he died, which may have contributed wholly or partly to the very high concentrations of organochlorines. CONCLUSION: Changes in weight must be recorded in cancer patients and the concentrations of persistent organic pollutants should be normalized to weight. The concentrations in this patient were 10- to almost 40-times higher than in the controls. Such very high concentrations may give clinical symptoms in the final stage of a wasting cancer patient.
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| 3. |
- Lauritzen, Märta, et al.
(författare)
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Intermittent self-dilatation after internal urethrotomy for primary urethral strictures : a case-control study
- 2009
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 43:3, s. 220-5
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To retrospectively evaluate the effects of intermittent self-dilatation (ISD) on the natural course of urethral strictures after an internal urethrotomy. MATERIAL AND METHODS: A retrospective case-control analysis of all males who had undergone a first time internal urethrotomy due to a urethral stricture in 1998-2000 at 15 urological departments in Sweden. Out of 217 included patients 162 were treated with internal urethrotomy only and 55 with internal urethrotomy followed by postoperative ISD. Demographic data including stricture localization, stricture aetiology and reoperation dates, as well as postoperative indwelling catheter and antibiotic treatment, were collected from the medical records. Factors concerning the ISD were also gathered: postoperative starting time, dilatation catheter size, dilatation frequency and time for retreatment. All patients' medical records were followed for 3-6 years until 2003. RESULTS: The median time until recurrence (surgical reoperation) was 732 days in the ISD group and 167 days in the non-ISD group (p<0.0001). The frequency of recurrence after internal urethrotomy was 9% (5/55) in the ISD group and 31% in the non-ISD group (51/162) during the observational follow-up period (p=0.0007). There was a higher risk of recurrence among those with a traumatic aetiology (39/104) compared with those with unknown aetiology (14/89) (p=0.0005). Patients with a postoperative catheter had a lower risk of recurrence (40/172) than those without one (16/45) (p=0.01). CONCLUSIONS: Postoperative ISD of a urethral stricture, primarily treated by internal urethrotomy, significantly reduces the stricture recurrence rate as well as delaying the time until recurrence.
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| 4. |
- Pawitan, Yudi, et al.
(författare)
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Gene expression profiling spares early breast cancer patients from adjuvant therapy : derived and validated in two population-based cohorts
- 2005
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Ingår i: Breast cancer research : BCR. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 7:6, s. R953-64
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Adjuvant breast cancer therapy significantly improves survival, but overtreatment and undertreatment are major problems. Breast cancer expression profiling has so far mainly been used to identify women with a poor prognosis as candidates for adjuvant therapy but without demonstrated value for therapy prediction. METHODS: We obtained the gene expression profiles of 159 population-derived breast cancer patients, and used hierarchical clustering to identify the signature associated with prognosis and impact of adjuvant therapies, defined as distant metastasis or death within 5 years. Independent datasets of 76 treated population-derived Swedish patients, 135 untreated population-derived Swedish patients and 78 Dutch patients were used for validation. The inclusion and exclusion criteria for the studies of population-derived Swedish patients were defined. RESULTS: Among the 159 patients, a subset of 64 genes was found to give an optimal separation of patients with good and poor outcomes. Hierarchical clustering revealed three subgroups: patients who did well with therapy, patients who did well without therapy, and patients that failed to benefit from given therapy. The expression profile gave significantly better prognostication (odds ratio, 4.19; P = 0.007) (breast cancer end-points odds ratio, 10.64) compared with the Elston-Ellis histological grading (odds ratio of grade 2 vs 1 and grade 3 vs 1, 2.81 and 3.32 respectively; P = 0.24 and 0.16), tumor stage (odds ratio of stage 2 vs 1 and stage 3 vs 1, 1.11 and 1.28; P = 0.83 and 0.68) and age (odds ratio, 0.11; P = 0.55). The risk groups were consistent and validated in the independent Swedish and Dutch data sets used with 211 and 78 patients, respectively. CONCLUSION: We have identified discriminatory gene expression signatures working both on untreated and systematically treated primary breast cancer patients with the potential to spare them from adjuvant therapy.
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