| 1. |
- Uggla, Bertil, 1962-, et al.
(författare)
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Expression of topoisomerase IIalpha in the G0/G1 cell cycle phase of fresh leukemic cells
- 2001
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Ingår i: Leukemia research. - Oxford, United Kingdom : Elsevier. - 0145-2126 .- 1873-5835. ; 25:11, s. 961-966
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Tidskriftsartikel (refereegranskat)abstract
- Topoisomerase IIalpha (topoII alpha) is the target enzyme for several antineoplastic drugs. Correlation between low expression of topo IIalpha and drug resistance has been shown in vitro, but there is limited evidence of a correlation to initial response to treatment or to overall prognosis. Normal cells express topo IIalpha in S/G2/M phase of the cell cycle but not in G0/G1 phase. However, some data suggest that topo IIalpha could be expressed in G0/G1 phase in malignant cells. We have investigated the expression of topo IIalpha in leukemic cells from 25 patients with acute leukemia by flow cytometry, separating cells of different cell cycle phases. We demonstrated that 9/25 samples showed >50% positive cells in G0/G1, and another five samples showed >20%. This finding could possibly provide an explanation to previous difficulties in correlating topo IIalpha expression with clinical outcome. Six of eight patients, where >20% of the cells in G0/G1 were positive for topo IIalpha, entered CR, compared to one of five patients with <20% topo IIalpha positive cells in G0/G1. We suggest that topo IIalpha expression in G0/G1 in leukemic cells may be of predictive value for clinical response to cytostatic drugs.
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| 2. |
- Akre [Fall], Katja, 1971-, et al.
(författare)
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Aspirin and risk for gastric cancer : a population-based case-control study in Sweden
- 2001
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Ingår i: British Journal of Cancer. - Edinburgh, United Kingdom : Churchill Livingstone. - 0007-0920 .- 1532-1827. ; 84:7, s. 965-8
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Tidskriftsartikel (refereegranskat)abstract
- While aspirin and other non-steroid anti-inflammatory drugs (NSAIDs) are associated with gastric mucosal damage, they might reduce the risk for gastric cancer. In a population-based case-control study in 5 Swedish counties, we interviewed 567 incident cases of gastric cancer and 1165 controls about their use of pain relievers. The cases were uniformly classified to subsite (cardia/non-cardia) and histological type and information collected on other known risk factors for gastric cancer. Helicobacter pylori serology was tested in a subset of 542 individuals. Users of aspirin had a moderately reduced risk of gastric cancer compared to never users; odds ratio (OR) adjusted for age, gender and socioeconomic status was 0.7 (95% CI = 0.6-1.0). Gastric cancer risk fell with increasing frequency of aspirin use (P for trend = 0.02). The risk reduction was apparent for both cardia and non-cardia tumours but was uncertain for the diffuse histologic type. No clear association was observed between gastric cancer risk and non-aspirin NSAIDs or other studied pain relievers. Our finding lends support to the hypothesis that use of aspirin reduces the risk for gastric cancer.
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| 3. |
- Bergström, A., et al.
(författare)
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Birth weight and risk of renal cell cancer
- 2001
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Ingår i: Kidney International. - Malden, USA : Blackwell Publishing. - 0085-2538 .- 1523-1755. ; 59:3, s. 1110-1113
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Tidskriftsartikel (refereegranskat)abstract
- Background: The prenatal period has been suggested to be important for future cancer risk. Conditions in utero are also important for the development of the kidney, and birth weight, a marker of fetal nutrition and growth, is linearly correlated with the number of nephrons and the structural and functional unit of the kidney. An association between birth weight and renal cell cancer, the major form of kidney cancer, is biologically plausible, but has never been studied.Methods: We conducted a population-based, case-controlled study in Sweden of men and women aged 20 to 79 years. We collected self-reported information on categories of birth weight from 648 patients with newly diagnosed renal cell cancer and from 900 frequency-matched control subjects. We used unconditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) as estimates of the relative risks.Results: An increased risk of renal cell cancer was observed among men with a birth weight of > or =3500 g (adjusted OR = 1.3, 95% CI, 1.0 to 1.8) compared with men with a birth weight between 3000 and 3499 g, especially in the subgroup without hypertension or diabetes (adjusted OR = 1.8, 95% CI, 1.2 to 2.6). No clear association among men with a birth weight <3000 g or among women was found.Conclusions: Our study shows that conditions in utero, reflected by birth weight, might affect the risk of renal cell cancer in adulthood. It is unclear why no association was found among women. Further studies, based on weight from birth certificates, are needed to clarify this relationship.
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| 4. |
- Bergström, A., et al.
(författare)
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Obesity and renal cell cancer : a quantitative review
- 2001
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Ingår i: British Journal of Cancer. - London, United Kingdom : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 85:7, s. 984-990
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Forskningsöversikt (refereegranskat)abstract
- Obesity has been associated with an increased risk of renal cell cancer among women, while the evidence for men is considered weaker. We conducted a quantitative summary analysis to evaluate the existing evidence that obesity increases the risk of renal cell cancer both among men and women. We identified all studies examining body weight in relation to kidney cancer, available in MEDLINE from 1966 to 1998. The quantitative summary analysis was limited to studies assessing obesity as body mass index (BMI, kg m(-2)), or equivalent. The risk estimates and the confidence intervals were extracted from the individual studies, and a mixed effect weighted regression model was used. We identified 22 unique studies on each sex, and the quantitative analysis included 14 studies on men and women, respectively. The summary relative risk estimate was 1.07 (95% CI 1.05-1.09) per unit of increase in BMI (corresponding to 3 kg body weight increase for a subject of average height). We found no evidence of effect modification by sex. Our quantitative summary shows that increased BMI is equally strongly associated with an increased risk of renal cell cancer among men and women.
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| 5. |
- Bergström, A., et al.
(författare)
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Physical activity and risk of renal cell cancer
- 2001
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Ingår i: International Journal of Cancer. - New York, USA : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 92:1, s. 155-157
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Tidskriftsartikel (refereegranskat)abstract
- The relation between physical activity and renal cell cancer is unclear. High occupational physical activity has been associated with a decreased risk of renal cell cancer among men-but not among women-in two previous studies, while no association has been found for leisure time physical activity. Our aim was to investigate the association between occupational and leisure time physical activity in a prospective cohort of 17,241 Swedish twins. Information on physical activity and a wide range of potential confounding factors was obtained through a mailed questionnaire. During follow-up from 1967 through 1997 we identified 102 cases of renal cell cancer. We found no evidence of an inverse association between either occupational or leisure time physical activity and risk of renal cell cancer in this prospective cohort.
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| 6. |
- Ma, X., et al.
(författare)
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VHL gene alterations in renal cell carcinoma patients : novel hotspot or founder mutations and linkage disequilibrium
- 2001
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Ingår i: Oncogene. - Hampshire, United Kingdom : Nature Publishing Group. - 0950-9232 .- 1476-5594. ; 20:38, s. 5393-5400
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in the von Hippel-Lindau (VHL) gene are frequently detected in human sporadic renal cell carcinoma (RCC). We analysed 102 Swedish RCCs for VHL mutations by PCR-SSCP and sequencing. In 47 patients (46.1%), 70 different mutations were found, and most of them represented novel variations of the VHL gene. Mutations in the VHL gene were found in 54% of clear cell renal cell carcinomas (CCRCC) and in 18% of chromophilic cancers but in no chromophobe cancers or oncocytomas (P=0.016). Three novel hotspot or founder mutations were detected in our study: four CCRCCs carried a missense mutation (glutamic acid to lysine) at codon 160 which is critical in the stabilization of the H1 helix of the alpha domain and the alpha-beta domain interface in the VHL protein. Five CCRCCs and one chromophilic RCC harbored a 15-nucleotide in-frame deletion (codons 41-45) at a duplex tandem repeat sequence site. Moreover, this deletion was in linkage disequilibrium with a C-->T transition in the promoter region. The frequency of linkage was 17 times more common than chance. Five patients with this linked mutation resided in the same hospital district and at least three of them showed the two sequence variants in the tumor-adjacent tissue. In 5/6 patients the wild-type allele was lost in the tumor samples, suggesting a causal role for the mutations in RCC. These linked mutations might be novel polymorphisms maintained in a relative isolated population. Multiple mutations in VHL were found in 17 tumors out of 47 tumors with the VHL mutation. A higher multiple mutation detected rate (33%) was observed in grade 3 CCRCCs than those in grade 1 (22%) and grade 2 (9%) (P=0.04). This is evidence on the association between VHL mutation and extent of nuclear atypia.
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