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- Berggren de Verdier, P. J., et al.
(author)
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Prognostic significance of homozygous deletions and multiple duplications at the CDKN2A (p16INK4a)/ARF (p14ARF) locus in urinary bladder cancer
- 2006
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In: Scand J Urol Nephrol. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 40:5, s. 363-9
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Journal article (peer-reviewed)abstract
- OBJECTIVE: The 9p21 locus is a major target in the pathogenesis of human urinary bladder cancer. This locus harbours the CDKN2A/ARF tumour suppressor gene, which encodes two cell-cycle regulatory proteins: p16INK4a and p14ARF. We studied how homozygous deletions and multiple duplications at this locus affect prognosis and survival in patients with bladder cancer. MATERIAL AND METHODS: Real-time quantitative polymerase chain reaction (QPCR), based on simultaneous amplification of ARF and a reference gene, glyceraldehyde-3-phosphate dehydrogenase, was used to measure homozygous deletions and multiple duplications in a population-based material consisting of 478 patients with urinary bladder cancer. Results from real-time QPCR were compared with clinico-pathological parameters and survival curves were generated using the Kaplan-Meier method. RESULTS: Real-time QPCR analysis showed 71 (15%) homozygous deletions and 8 (2%) multiple duplications. We were unable to find any association between either stage or grade and urinary neoplasms with homozygous deletions. However, although there were only a limited number of patients with multiple duplications, 7/8 of them had highly malignant tumours (G2b-G4 or > or = T1; p = 0.02). CONCLUSIONS: Urinary bladder cancers constitute a spectrum of neoplasms with varying clinical manifestations. We were unable to establish a prognostic relevance for patients with tumours harbouring homozygous deletions at the CDKN2A/ARF locus. However, our data did indicate that patients with multiple duplications at the CDKN2A/ARF locus had poor survival. This suggests that multiple duplications, in combination with other genetic changes, have cooperative effects which have a negative outcome on urinary bladder cancer prognosis.
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- Berggren, P, et al.
(author)
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p53 mutations in urinary bladder cancer
- 2001
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In: British journal of cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 84:11, s. 1505-1511
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Journal article (peer-reviewed)
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- Hansson, Erik, 1987, et al.
(author)
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Markers of kidney tubular and interstitial injury and function among sugarcane workers with cross-harvest serum creatinine elevation
- 2022
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In: Occupational and Environmental Medicine. - : BMJ. - 1470-7926 .- 1351-0711. ; 79:6, s. 396-402
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Journal article (peer-reviewed)abstract
- Objectives Serum creatinine (SCr) is a routine marker of kidney injury but also increases with dehydration and muscular work. This study was to elucidate whether increase in SCr is associated with more specific markers of kidney tubular and interstitial injury and function, during prolonged heat stress among workers at high risk of chronic kidney disease of non-traditional origin (CKDnt). Methods Urine monocyte chemoattractant protein-1 (MCP-1), kidney injury molecule-1 (KIM-1), calbindin, glutathione S-transferase-pi (GST-pi), clusterin, interleukin 18 and albumin, fractional excretion of potassium (FEK), blood haemoglobin, serum potassium, ferritin and erythropoietin were measured before and after harvest in a sample of 30 workers with a >= 0.3 mg/dL SCr increase across harvest (cases), and 53 workers with stable SCr (controls). Results Urine MCP-1 (p for differential cross-harvest trend <0.001), KIM-1 (p=0.002), calbindin (p=0.02), GST-pi (p=0.04), albumin (p=0.001) and FEK (p<0.001) increased in cases, whereas blood haemoglobin (p<0.001) and serum erythropoietin (p<0.001) decreased. Conclusion Several markers of tubular and interstitial injury and function changed as SCr increased across a harvest season, supporting the use of SCr as an indicator of kidney injury in physically active workers regularly exposed to heat stress. Repeated injury similar to that described here, and continued work under strenuous and hot conditions with similarly elevated injury markers is likely to worsen and possibly initiate CKDnt.
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- Hardell, L, et al.
(author)
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Concentrations of polychlorinated biphenyls in blood and the risk for testicular cancer
- 2004
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In: International Journal of Andrology. - : Wiley. - 0105-6263 .- 1365-2605. ; 27:5, s. 282-290
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Journal article (peer-reviewed)abstract
- An increasing incidence of testicular cancer has been reported from several western countries during the last decades. According to current hypothesis testicular cancer is initiated during the foetal period and exposure to endocrine disruptors such as some persistent organic pollutants has been of concern. We have previously reported the results for concentrations of polychlorinated biphenyls (PCBs), p,p'-dichlorodiphenyl-dichloroethylene (pp'-DDE), hexachlorobenzene (HCB) and chlordanes in 58 cases with testicular cancer, 61 age-matched controls and 44 case mothers and 45 control mothers. In that report, significant increase of odds ratio (OR) was found for sum of PCBs, HCB, trans- and cis-nonachlordane in case mothers. These data have now been further analysed for 37 congeners of PCBs. No significant differences were found among cases and controls. However, case mothers had significantly increased concentrations of a number of PCB congeners. A priori decided grouping of PCBs yielded for oestrogenic PCBs OR = 2.4, 95% confidence interval (CI) = 0.95-6.0, enzyme-inducing PCBsOR = 2.6, 95% CI = 1.03-6.5 and toxic equivalents (TEQ) yielded OR = 3.3, 95% CI = 1.3-8.4. These data further elucidate the role of foetal exposure to different PCB congeners in the aetiology of testicular cancer.
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- Hardell, L, et al.
(author)
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Increased concentrations of polychlorinated biphenyls, hexachlorobenzene, and chlordanes in mothers of men with testicular cancer
- 2003
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In: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 111:7, s. 930-934
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Journal article (peer-reviewed)abstract
- An increasing incidence of testicular cancer has been reported from several countries in the Western world during the last decades. According to current hypothesis, testicular cancer is initiated during the fetal period, and exposure to endocrine disruptors, i.e., xenoestrogens, has been of concern. In this investigation we studied the concentrations of the sum of 38 polychlorinated biphenyls (PCBs), p,p'-dichlorodiphenyl-dichloroethylene, hexachlorobenzene (HCB), and chlordanes, in 61 cases with testicular cancer and 58 age-matched controls. Furthermore, case and control mothers were also asked to participate, and 44 case mothers and 45 control mothers agreed. They were of similar age. In cases only the concentration on lipid basis of cis-nonachlordane was significantly increased, whereas case mothers showed significantly increased concentrations of the sum of PCBs, HCB, trans- and cis-nonachlordane, and the sum of chlordanes. Among case mothers the sum of PCBs yielded an odds ratio (OR) of 3.8, 95% confidence interval (CI), 1.4-10 was calculated using the median concentration for the control mothers as cutoff value. For HCB, OR = 4.4 (95% CI, 1.7-12), for trans-nonachlordane, OR = 4.1 (95% CI, 1.5-11), for cis-nonachlordane, OR = 3.1 (95% CI, 1.2-7.8), and for sum of chlordanes, OR = 1.9 (95% CI, 0.7-5.0). No consistent different risk pattern was found for seminoma. or nonseminoma testicular cancer.
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- Henningsohn, L, et al.
(author)
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Relative importance of sources of symptom-induced distress in urinary bladder cancer survivors
- 2003
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In: European Urology. - 0302-2838 .- 1873-7560. ; 43:6, s. 651-662
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Journal article (peer-reviewed)abstract
- Objective: The influence of specific symptoms on emotions and social activities in the individual patient vanes. Little is known about this variation in urinary bladder cancer survivors (in other words, about the relative importance of sources of symptom-induced distress). Methods: We attempted to enrol 404 surgical patients treated with cystectomy and a conduit or reservoir in four Swedish towns (Stockholm, Orebro, Jonkoping, Linkoping), 101 surgical patients treated with cystectomy and orthotopic neobladder at the Herlev Hospital in Copenhagen, Denmark, and 71 patients treated with radical radiotherapy for bladder cancer, as well as 581 men and women controls in Stockholm and Copenhagen. An anonymous postal questionnaire was used to collect the information. Results: A total of 503 out of 576 (87%) treated patients and 422 out of 581 (73%) controls participated but 59 patients were excluded. The primary source of self-assessed distress among cystectomised patients was compromised sexual function, reduced intercourse frequency caused great distress in 19% of the conduit patients, 20% of the reservoir patients and 19% of the bladder substitute patients. The primary source of self-assessed distress in patients treated with radical radiotherapy was symptoms from the bowel, 17% reported great distress due to diarrhoea, 16% due to abdominal pain, 14% due to defecation urgency and 14% due to faecal leakage. The highest proportion of subjects being distressed was 93% (substantial: 43%, moderate: 29% and little: 21%) for treated upper or lower urinary retention (indwelling catheter or nephrostomy). Conclusion: The distress caused by a specific symptom varies considerably and the prevalence of symptoms causing great distress differs between treatments in bladder cancer survivors. It is possible that patient care and clinical research can be made more effective by focusing on important sources of symptom-induced distress. (C) 2003 Elsevier Science B.V. All rights reserved.
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- Kaasinen, E, et al.
(author)
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Alternating mitomycin C and BCG instillations versus BCG alone in treatment of carcinoma in situ of the urinary bladder: A Nordic study
- 2003
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In: European Urology. - 1873-7560. ; 43:6, s. 637-645
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Journal article (peer-reviewed)abstract
- Objectives: To evaluate whether, in patients with carcinoma in situ (CIS) of the urinary bladder, alternating instillation therapy with mitomycin C (MMC) and bacillus Calmette-Guerin (BCG) was more effective and less toxic than conventional BCG monotherapy. Methods: Patients were stratified prospectively for primary, secondary, and concomitant CIS and randomized to one of two regimens. Patients in the alternating group received six weekly intravesical instillations of MMC 40 mg, followed by alternating monthly instillations of BCG 120 mg and MMC for one year. In the monotherapy group, only BCG was instilled on the same schedule. Results: Of 323 enrolled patients, 304 were eligible for analysis. After an overall median follow-up of 56 months, the Kaplan-Meier disease-free estimate for BCG monotherapy was significantly better than that for alternating therapy (p = 0.03; log rank test). Risk for progression appeared lower in the BCG monotherapy group (p = 0.07) but no differences existed in survival. Besides the regimen, CIS category also predicted outcome to some extent. BCG monotherapy caused significantly more local side-effects and premature cessation of instillation treatment than did the alternating therapy. However, no differences were observed in the number of serious side-effects. Conclusion: One-year BCG monotherapy was more effective than the alternating therapy for reducing recurrence and compared well with the best regimens reported from substantially smaller series. The alternating therapy was better tolerated.
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