| 1. |
- Alexander, F. E.
(author)
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Rationale for randomised trials of prostate cancer screening
- 1999
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In: European Journal of Cancer. - 0959-8049. ; 35:2, s. 262-271
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Research review (peer-reviewed)abstract
- Screening for prostate cancer has been advocated by a number of organisations largely because there is good evidence that administration of the test for prostate specific antigen (PSA) results in the detection of cancers at an early stage. However, the mere fact that a cancer can be detected earlier in its natural history by screening is no guarantee that benefit will follow. Further, screening for prostate cancer can substantially impair the quality of life of those with detected and treated cancer, that would not otherwise have reduced life expectancy. The only established mechanism to evaluate the efficacy of screening is the randomised controlled trial. In this paper we review the trials contributing to our collaboration, the advantages that will flow from them, and the reasons why decisions on the introduction of population-based screening for prostate cancer cannot be made before these trials have come to fruition.
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| 2. |
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| 3. |
- Olsson, I, et al.
(author)
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Cell differentiation in acute myeloid leukemia
- 1996
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In: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 57:1, s. 1-16
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Research review (peer-reviewed)abstract
- Acute myeloid leukemia (AML) is characterized by a differentiation block leading to accumulation of immature cells. Chromosomal translocations in AML affect transcription factors that are involved in regulation of myeloid differentiation. Aberrant expression of these factors interferes with differentiation events and has a role in the pathogenesis of AML through superactivation or (dominant negative) repression of genes regulating proliferation and differentiation or by interference with assembly of the transcription complex for these genes. The maturation arrest can be reversed by certain agents as judged by results from investigations of myeloid leukemic cell lines and from treatment of acute promyelocytic leukemia (APL) patients with all-trans retinoic acid. Inactivation of the p53 and retinoblastoma (Rb) tumor suppressor genes is also associated with the pathogenesis of leukemia through effects on the cell cycle, and manipulation of these genes can affect differentiation of AML cells. With differentiation therapy, when successful as in APL, the leukemic cell mass is reduced to allow restoration of normal hematopoiesis and clinical remission, but the disease is not cured. However, initial reduction of the cell mass by maturation can increase the probability for cure with chemotherapy. Overexpression of suppressor genes may increase the probability for differentiation. Most probably, particular molecular defects of subgroups of AML have to be explored to find optimal strategies for treatment including both blocking the cell cycle, promoting terminal differentiation, and inducing apoptosis as well as strengthening the immune response.
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| 4. |
- Dictor, Michael, et al.
(author)
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Abnormal cell cycle regulation in malignancy
- 1999
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In: American Journal of Clinical Pathology. - 0002-9173. ; 112:1 Suppl 1, s. 40-52
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Research review (peer-reviewed)abstract
- The cell cycle consists of an initial growth phase (G1), DNA replication (S), a gap phase (G2), and mitosis (M), after which the cell may differentiate or enter the resting state (G0). The cycle is driven by a number of positive and negative regulatory phosphorylation and dephosphorylation events, involving protein kinases, protein phosphatases, cyclins, cyclin-dependent kinases, and cyclin-dependent kinase inhibitors, that ultimately impinge on the activity of transcription factors. Unreplicated or damaged DNA blocks the progression of the cell cycle at checkpoints, including a late G1 checkpoint regulated by the dephosphorylated retinoblastoma protein and a late G2 checkpoint regulated by the phosphorylation of cyclin-dependent kinase 1 complexed with cyclin B. Many cell cycle regulator genes may be considered proto-oncogenes or tumor suppressor genes, and point mutations, amplifications, deletions, or rearrangements involving their loci, particularly those in the "RB pathway," are associated with various tumors. A number of molecular techniques may be used to detect genomic alterations or posttranscriptional modifications, but immunohistochemistry remains the most common method to determine expression levels of a regulatory protein. Multivariate analysis of the usefulness in prognosis has been applied most often for the general proliferation antigen Ki-67.
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| 5. |
- Khan, J, et al.
(author)
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Expression profiling in cancer using cDNA microarrays
- 1999
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In: Electrophoresis. - 0173-0835. ; 20:2, s. 223-229
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Research review (peer-reviewed)abstract
- Currently there are over 1,000,000 human expressed sequence tag (EST) sequences available on the public database, representing perhaps 50-90% of all human genes. The cDNA microarray technique is a recently developed tool that exploits this wealth of information for the analysis of gene expression. In this method, DNA probes representing cDNA clones are arrayed onto a glass slide and interrogated with fluorescently labeled cDNA targets. The power of the technology is the ability to perform a genome-wide expression profile of thousands of genes in one experiment. In our review we describe the principles of the microarray technology as applied to cancer research, summarize the literature on its use so far, and speculate on the future application of this powerful technique.
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| 6. |
- Wolk, A., et al.
(author)
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Nutrition and renal cell cancer
- 1996
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In: Cancer Causes and Control. - London, United Kingdom : Rapid Science Publisher. - 0957-5243 .- 1573-7225. ; 7:1, s. 5-18
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Research review (peer-reviewed)abstract
- Epidemiologic evidence on the relation between nutrition and renal cell cancer is reviewed. Kidney cancer, comprising 1.7 percent of all malignant diseases diagnosed worldwide, shows about a 20-fold international variation in the incidence in men and 10-fold in women. This substantial variation indicates an important causal role of environmental factors. Renal cell (parenchymal) cancer (RCC) accounts for about 80 percent of all kidney cancers. While the etiology of RCC is incompletely understood, analytic epidemiologic studies provide consistent support for a positive association of obesity with risk of RCC; the dose-response observed supports a causal relationship. Only a few prospective studies, all of them limited in size, have been published, while ecologic and case-control studies suggest that diet may be important in the etiology of RCC. However, contradictory results and methodologic limitations in some case-control studies prevent definite conclusions concerning diet and RCC. A positive association of protein and fat intake, as well as their main food sources (meat, milk, fats), with risk of RCC-as suggested by ecologic studies-has no clear support in analytic epidemiologic studies. A protective effect of vegetables and fruits has been observed in most case-control studies, while the majority do not show an association between alcohol, coffee, and risk of RCC. Recent reports indicated an increased risk of RCC associated with consumption of fried/sauteed meat and low intakes of magnesium or vitamin E. An apparent positive association with total energy intake, perhaps due to bias, needs further investigation.
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