| 81. |
- Haglund, Mattias, et al.
(författare)
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Cerebral amyloid angiopathy, white matter lesions and Alzheimer encephalopathy - A histopathological assessment
- 2002
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 14:3, s. 161-166
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Tidskriftsartikel (refereegranskat)abstract
- To test the hypothesis that the cerebral amyloid angiopathy (CAA) of Alzheimer's disease (AD) is quantitatively associated with white matter lesions (WML), the brains of 63 demented patients exhibiting varying degrees of Alzheimer encephalopathy (AE) were examined, along with those of 10 nondemented control cases. The ratio of amyloid-positive to amyloid-negative vessels in the leptomeninges of the frontal pole from each patient was calculated subsequent to microscopical examination, and the severity of WML was graded according to previously published criteria. In AD cases without a significant component of vascular dementia, the level of CAA was found to correlate with the degree of WML diagnosed and graded by neuropathology. Neither age nor severity of AE correlated significantly with WML. There may be several reasons for the conflicting results of this study vis-a-vis earlier investigations; the roles played by different methods of staining, CAA quantitation and patient subgroup selection are also discussed. Copyright (C)2002 S. Karger AG, Basel.
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| 82. |
- Hardell, Lennart, et al.
(författare)
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Exposure to pesticides as risk factor for Non-Hodgkin's lymphoma and hairy cell leukemia : Pooled analysis of two Swedish case-control studies
- 2002
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Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 43:5, s. 1043-1049
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Tidskriftsartikel (refereegranskat)abstract
- Increased risk for non-Hodgkin's lymphoma (NHL) following exposure to certain pesticides has previously been reported. To further elucidate the importance of phenoxyacetic acids and other pesticides in the etiology of NHL a pooled analysis was performed on two case-control studies, one on NHL and another on hairy cell leukemia (HCL), a rare subtype of NHL. The studies were population based with cases identified from cancer registry and controls from population registry. Data assessment was ascertained by questionnaires supplemented over the telephone by specially trained interviewers. The pooled analysis of NHL and HCL was based on 515 cases and 1141 controls. Increased risks in univariate analysis were found for subjects exposed to herbicides (OR 1.75, CI 95% 1.26-2.42), insecticides (OR 1.43, CI95% 1.08-1.87), fungicides (OR 3.11, CI 95% 1.56-6.27) and impregnating agents (OR 1.48, CI 95% 1.11-1.96). Among herbicides, significant associations were found for glyphosate (OR 3.04, CI 95% 1.08-8.52) and 4-chloro-2-methyl phenoxyacetic acid (MCPA) (OR 2.62, CI 95% 1.40-4.88). For several categories of pesticides the highest risk was found for exposure during the latest decades before diagnosis. However, in multivariate analyses the only significantly increased risk was for a heterogeneous category of other herbicides than above.
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| 83. |
- Hardy, J, et al.
(författare)
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A double-blind, randomised, parallel group, multinational, multicentre study comparing a single dosed of ondansetron 24 mg p.o. with placebo and metoclopramide 10 mg t.d.s. p.o. in the treatment of opioid-induced nausea and emesis in cancer patients
- 2002
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Ingår i: Supportive Care in Cancer. - : Springer Science and Business Media LLC. - 0941-4355 .- 1433-7339. ; 10:3, s. 231-236
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Tidskriftsartikel (refereegranskat)abstract
- Nausea and emesis are common side effects of opioid drugs administered for pain relief in cancer patients. The aim of this study was to compare the anti-emetic efficacy and safety of ondansetron, placebo and metoclopramide in the treatment of opioid-induced nausea and emesis (OIE) in cancer patients. This was a multinational, multicentre, double-blind, parallel group study in which cancer patients who were receiving a full opioid agonist for cancer pain were randomised to receive one of oral ondansetron 24 mg once daily, metoclopramide 10 mg three times daily, or placebo. Study medication was started only if the patient experienced nausea and/or emesis following opioid administration. Efficacy and safety assessments were made over a study period of 24 h from the time of the first dose of anti-emetics/placebo. The study was terminated prematurely because of the difficulties in recruiting patients satisfying the stringent entry criteria. Ninety-two patients were included in the intent-to-treat population: 30 patients received placebo, 29 patients ondansetron and 33 patients metoclopramide. There was no statistically significant difference between the groups in the proportion achieving complete control of emesis (33% of patients on placebo. 48% on ondansetron and 52% on metoclopramide) or complete control of nausea (23% of patients on placebo. 17% on ondansetron and 36% on metoclopramide). Rescue anti-emetics were required in 8 of 33 patients on metoclopramide, 4 of 29 on ondansetron, and 3 of 30 on placebo. The incidence of adverse events was very low and similar in all treatment groups. Neither ondansetron 24 mg once daily nor metoclopromide 10 mg t.d.s. given orally was significantly more effective than placebo in the control of OIE in cancer patients.
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| 84. |
- Haugen, Hedda, 1970, et al.
(författare)
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Hyperfractionated-accelerated or conventionally fractionated radiotherapy for early glottic cancer.
- 2002
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Ingår i: International journal of radiation oncology, biology, physics. - 0360-3016. ; 52:1, s. 109-19
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To evaluate the effect of shortening overall treatment time by hyperfractionated-accelerated radiotherapy for T2N(0)M(0) glottic carcinomas. Results for local control and survival were calculated and compared to those for T1N(0)M(0) tumors treated with a once-a-day fractionated schedule. METHODS AND MATERIALS: Between 1990 and 1998, 92 patients with T1N(0)M(0) and 45 patients with T2N(0)M(0) glottic cancers were treated with radical radiotherapy. The T1N(0)M(0) tumors were treated with a once-a-day fractionated schedule lasting 6.5 weeks to a total dose of 62.4 Gy. The T2N(0)M(0) tumors received a split-course hyperfractionated-accelerated treatment over a total of 4.5 weeks to a total dose of 64.6 Gy.Results: The 5-year local control was 85% for T1N(0)M(0) and 88% for T2N(0)M(0), whereas the 5-year locoregional control was 85% for both groups. The 5-year overall survival was 70% and 53% for T1N(0)M(0) and T2N(0)M(0), respectively. No significant statistical difference was found between the two groups for the parameters analyzed. The number of serious late complications was few and comparable for the two groups. CONCLUSIONS: Hyperfractionated-accelerated radiotherapy proved beneficial for T2N(0)M(0) glottic cancer, giving local control rates comparable to those for T1N(0)M(0) tumors.
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| 85. |
- Hedberg, Y, et al.
(författare)
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Cyclin D3 protein content in human renal cell carcinoma in relation to cyclin D1 and clinico-pathological parameters
- 2002
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 41:2, s. 175-181
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Tidskriftsartikel (refereegranskat)abstract
- Aberrations in the G1/S checkpoint are common in malignancies and are probably important for tumor development. Few G1/S studies have been performed on renal cell carcinoma (RCC) and therefore in this study the cyclin D3 protein content in 80 RCCs and that in 12 corresponding normal kidney cortex tissues are characterized using Western blotting. High cyclin D3 protein content was observed in 16% of the tumors and was significantly associated with aneuploidy, high TNM stage, high nuclear grade, high proliferation and young age. There was no association between tumor cyclin D3 and patient survival. The cyclin D3 overexpression was confirmed by immunohistochemical staining of 72 tumors, showing both nuclear and cytoplasmic localization of cyclin D3 in a fraction of the tumors. The cyclin D1 content has earlier been characterized in this tumor material and there was no relation between cyclin D1 and cyclin D3 protein expression. In summary, a fraction of the tumors overexpressed cyclin D3, supporting that various aberrations in the G1/S transition are implicated in RCCs.
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| 86. |
- Hedberg, Y, et al.
(författare)
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Cyclin E and P27 protein content in human renal cell carcinoma: Clinical outcome and associations with cyclin D
- 2002
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 102:6, s. 601-607
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Tidskriftsartikel (refereegranskat)abstract
- Aberrations in the GI-S transition have been observed in several malignancies, suggesting that cell cycle defects are linked to the activation of oncogenes and inactivation of suppressor genes involved in the transformation process. The frequency of GI/S aberrations in human renal cell carcinoma (RCC) has not been fully clarified. We have therefore analyzed the cyclin E content, using Western blotting, in 79 RCC and 12 corresponding kidney cortex tissues as well as the fraction of p27-positive cells in 73 RCCs, using immunohistochemistry. Most of the tumors (65%) exhibited higher cyclin E levels than corresponding normal kidney cortex tissues. However, only a small fraction of the tumors (3 of 80) had excessive levels of cyclin E when cyclin E levels were compared with proliferation. Cyclin E levels higher than the median value were associated with aneuploicly (p = 0.025), high stage (p = 0.027), high grade (p = 0.013) and high erythrocyte sedimentation rate (ESR; p = 0.005). Cyclin E was further inversely correlated with cyclin D1 (p = 0.023) and positively correlated with cyclin D3 (p = 0.003). Most tumors (76%) demonstrated a normal fraction of p27-positive cells. There was an inverse correlation between p27 positivity and tumor size (p = 0.007), despite a lack of correlation between p27 and proliferation. Patients with p27 low tumors had a poor survival (p = 0.002). There was no correlation between p27 and cyclin E levels. In summary, the results suggest that protein expression of cyclin E and/or p27 is linked to tumor behavior. (C) 2002 Wiley-Liss, Inc.
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| 87. |
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| 88. |
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| 89. |
- Hegardt, Cecilia, et al.
(författare)
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Rapid caspase-dependent cell death in cultured human breast cancer cells induced by the polyamine analogue N-1,N-11-diethylnorspermine
- 2002
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Ingår i: European Journal of Biochemistry. - : Wiley. - 0014-2956. ; 269:3, s. 1033-1039
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Tidskriftsartikel (refereegranskat)abstract
- The spen-nine analogue N-1,N-11-diethylnorspermine (DENSPM) efficiently depletes the cellular pools of putrescine, spermidine and spermine by down-regulating the activity of the polyamine biosynthetic enzymes and up-regulating the activity of the catabolic enzyme spermidine/spermine N-1-acetyltransferase (SSAT). In the breast cancer cell line L56Br-Cl. treatment with 10 muM DENSPM induced SSAT activity 60 and 240-fold at 24 and 48 h after seeding. respectively, which resulted in polyamine depletion. Cell proliferation appeared to be totally inhibited and within 48 h of treatment, there was an extensive apoptotic response. Fifty percent of the cells were found in the sub-G(1) region, as determined by flow cytometry, and the presence of apoptotic nuclei was morphologically assessed by fluorescence microscopy. Caspase-3 and caspase-9 activities were significantly elevated 24 h after seeding, At 48 h after seeding, caspase-3 and caspase-9 activities were further elevated and at this time point a significant activation of caspase-8 was also found. The DENSPM-induced cell death was dependent on the activation of the caspases as it was inhibited by the general caspase inhibitor Z-Val-Ala-Asp fluoromethyl ketone. The results are discussed in the fight of the L56Br-Cl cells containing mutated BRCA1 and p53, two genes involved in DNA repair.
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| 90. |
- Hemminki, K., et al.
(författare)
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Molecular epidemiology of VHL gene mutations in renal cell carcinoma patients : relation to dietary and other factors
- 2002
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Ingår i: Carcinogenesis. - Oxford, United Kingdom : Oxford University Press. - 0143-3334 .- 1460-2180. ; 23:5, s. 809-815
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Tidskriftsartikel (refereegranskat)abstract
- Carcinogenic chemicals act through DNA damage and mitogenic effects. No established mechanism explains the cancer preventive effects, if any, of food items, such as vegetables and fruit. If such data were available, preferably on tumor-initiating genes, the evidence for the protective effects would become stronger. The von Hipple-Lindau (VHL) gene is the tumor suppressor gene predisposing to both sporadic renal cell carcinoma (RCC) and von Hippel-Lindau disease. We have earlier analyzed VHL mutations in RCCs from 102 Swedish patients identified in a case-control study and here examine associations between patient characteristics, including dietary habits and mutations, considering the type of mutation. The results are given as odds ratios (OR), separately for smokers and all patients. In univariate analysis, consumption of vegetables and citrus fruit decreased the frequency of VHL mutations among smokers and citrus fruit among all patients. In multivariate analysis of smokers' characteristics, welding fumes showed a risk of 5.63 for multiple VHL mutations. In smokers, citrus fruit decreased the OR of GC to AT mutations to 0.13 and that of multiple mutations to 0.17; vegetables decreased the OR for single mutations to 0.22. Among all subjects, welding fumes were a risk factor and citrus fruit a protective factor. Additionally, an intake of selenium protected against multiple mutations. The present results provide evidence that the intake of vegetables, selenium and particularly of citrus fruit protects the renal VHL gene from mutational insults that may be endogenous or common in a population. Even though most of the associations are biologically plausible, and vegetables and fruit were an a priori hypothesis, fortuitous results cannot be ruled out in this relatively small study.
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