| 21. |
- Benetkiewicz, Magdalena, et al.
(författare)
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Identification of limited regions of genetic aberrations in patients affected with Wilms' tumor using a tiling-path chromosome 22 array
- 2006
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 119:3, s. 571-578
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Tidskriftsartikel (refereegranskat)abstract
- Wilms' tumor (WT) is one of the most common solid tumors of childhood. The genetics of this disorder is complex and few studies have suggested allelic loss of chromosome 22 as a frequent aberration. To assess tumor- and possible germline-specific regions affected with gene copy number variations on this chromosome, we applied a high-resolution genomic clone-based chromosome 22 array to a series of 28 WT samples and the paired blood-derived DNA of the patients. The group of tumors was enriched for cases with metastases, relapse or fatal outcome, criteria that were expected to yield a higher number of alterations on chromosome 22. Overall, the array-based form of comparative genomic hybridization (array-CGH) analysis revealed genomic changes in 53% (15 out of 28) of cases. We identified hemizygous deletion of the whole arm of 22q in 3 tumors (11%). Furthermore, a complex amplifier genotype was detected in 8 samples, presenting regions of gain along the chromosome, which defined 7 distinct minimal overlapping segments. The distribution of aberrations in 4 additional cases displaying regional genomic imbalances delimited 2 tumor suppressor/oncogene candidate loci, 1 in the proximal and the other in the terminal part of 22q. Analysis of these regions revealed the presence of several candidate genes that may play a role in the development of WT. These findings demonstrate the power of array-CGH in the determination of DNA copy number alterations and further strength the notion that WT-associated genes exist on this chromosome.
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| 22. |
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| 23. |
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| 24. |
- Berndtsson, Maria, et al.
(författare)
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Induction of the lysosomal apoptosis pathway by inhibitors of the ubiquitin-proteasome system
- 2009
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 124:6, s. 1463-1469
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Tidskriftsartikel (refereegranskat)abstract
- The lysosomal apoptosis pathway is a potentially interesting therapeutic target. Since apoptosis involving the lysosomal pathway has been described to involve cathepsins, we screened a drug library for agents that induce cathepsin-dependent apoptosis. Using pharmacological inhibitors and siRNA, we identified 2 structurally related agents (NSC687852 and NSC638646) that induced cathepsin D-dependent caspase-cleavage activity in human breast cancer cells. Both agents were found to induce the mitochondrial apoptosis pathway. NSC687852 and NSC638646 were found to inhibit the activity of ubiquitin isopeptidases and to induce the accumulation of high-molecular-mass ubiquitins in cells. We show that 3 other inhibitors of the proteasome degradation pathway induce lysosomal membrane permeabilization (LMP) and that cathepsin-D siRNA inhibits apoptosis induced by these agents. We conclude that a screen for cathepsin-dependent apoptosis-inducing agents resulted in the identification of ubiquitin isopeptidase inhibitors and that proteasome inhibitors with different mechanisms of action induce LMP and cathepsin D-dependent apoptosis.
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| 25. |
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| 26. |
- Beskow, Anna H., et al.
(författare)
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Interaction of host and viral risk factors for development of cervical carcinoma in situ
- 2005
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 117:4, s. 690-692
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Infection by oncogenic human papillomavirus (HPV) is a necessary but not sufficient cause of cervical carcinoma. Several host genetic and viral factors have been reported to increase the risk of carcinoma development given an HPV infection. In our study, we have analysed the contribution of HPV 16 E6 sequence subtype and allelic variation at human leukocyte antigen (HLA) class II loci to the risk of developing cervical carcinoma in situ. Non-European-like HPV 16 E6 sequence subtypes were not found to be associated with an increased risk of cervical carcinoma, as compared to European-like variants. However, an association was found between the HPV 16 E6 L83V variant and the DR*04-DQ*03 haplotype. This association has been observed in several independent studies and shows that both the host HLA class II genotype and viral subtype will affect the risk of an infection progressing into cervical carcinoma.
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| 27. |
- Bexell, Daniel, et al.
(författare)
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CD133+ and nestin+ tumor-initiating cells dominate in N29 and N32 experimental gliomas.
- 2009
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 125:1, s. 15-22
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Tidskriftsartikel (refereegranskat)abstract
- The current study was designed to critically evaluate the notion that cancer stem cell (CSC)-like cells constitute a subpopulation of cells within experimental gliomas. Virtually all cells within the N29 and N32 rat glioma models homogenously expressed CD133, the stem/progenitor marker nestin as well as the neural lineage markers glial fibrillary acidic protein, betaIII-tubulin, and CNPase in vitro. The phenotype was largely retained on exposure to conditions promoting differentiation in vitro and after intracranial implantation of tumor cells into syngeneic hosts. Unsorted adherently grown cells displayed very high clonogenicity in vitro and robust tumorigenicity in vivo. Single N29 and N32 tumor cells invariably formed clones in vitro, and intracerebral inoculation of as few as 10 adherently growing N29 and N32 tumor cells, respectively, gave rise to a tumor. These results provide an alternative view on CSC-like cells in glioma models: sphere-formation is not a prerequisite for accumulation of tumorigenic cells, and CSC-like cells do not reside within a rare subpopulation of cells in these glioma models. N29 and N32 gliomas may accordingly be used for the development of treatment strategies directed specifically against a practically pure population of brain tumor-initiating CSC-like cells. (c) 2009 Wiley-Liss, Inc.
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| 28. |
- Biggar, Robert J., et al.
(författare)
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Immunoglobulin subclass levels in patients with non-Hodgkin lymphoma
- 2009
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 124:11, s. 2616-20
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Tidskriftsartikel (refereegranskat)abstract
- Allergy/atopy has been suggested to protect against non-Hodgkin lymphoma (NHL) and specific IgE levels are decreased in patients with NHL. We speculated that all immunoglobulin subclass levels might be downregulated in NHL and examined levels of IgM, IgD, IgA, IgE, IgG and IgG(4) in 200 NHL patients and 200 age- and sex-matched controls. Patients with B-cell NHL of many types had consistently lower median immunoglobulin subclass levels than controls. In every subclass except IgD, about 10-15% of B-cell NHL patients had absolute levels below the 2.5 percentile of controls. Subclass levels correlated with each other and many patients had more than one significantly low level. Levels were lowest for IgG(4) and IgE. Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma had especially low total IgE levels. In other B-cell NHL types, total IgE levels were decreased to a similar extent as other immunoglobulin subclasses. In conclusion, low IgE levels are only part of a more generalized loss of immunoglobulins of all subtypes in a wide variety of B-cell NHL types. Low immunoglobulin levels appear to be a consequence of B-cell NHL presence, and we speculate about molecular mechanisms that could reduce all immunoglobulin subclasses in B-cell NHL.
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| 29. |
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| 30. |
- Bistoletti, P., et al.
(författare)
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Cost-effectiveness of primary cytology and HPV DNA cervical screening
- 2008
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 122:2, s. 372-376
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Tidskriftsartikel (refereegranskat)abstract
- Because cost-effectiveness of different cervical cytology screening strategies with and without human papillomavirus (HPV) DNA testing is unclear, we used a Markov model to estimate life expectancy and health care cost per woman during the remaining lifetime for 4 screening strategies: (i) cervical cytology screening at age 32, 35, 38, 41, 44, 47, 50, 55 and 60, (ii) same strategy with addition of testing for HPV DNA persistence at age 32, (iii) screening with combined cytology and testing for HPV DNA persistence at age 32, 41 and 50, iv) no screening. Input data were derived from population-based screening registries, health-service costs and from a population-based HPV screening trial. Impact of parameter uncertainty was addressed using probabilistic multivariate sensitivity analysis. Cytology screening between 32 and 60 years of age in 3-5 year intervals increased life expectancy and life-time costs were reduced from 533 to 248 US Dollars per woman compared to no screening. Addition of HPV DNA testing, at age 32 increased costs from 248 to 284 US Dollars without benefit on life expectancy. Screening with both cytology and HPV DNA testing, at ages 32, 41 and 50 reduced costs from 248 to 210 US Dollars with slightly increased life expectancy. In conclusion, population-based, organized cervical cytology screening between ages 32 to 60 is highly cost-efficient for cervical cancer prevention. If screening intervals are increased to at least 9 years, combined cytology and HPV DNA screening appeared to be still more effective and less costly. © 2007 Wiley-Liss, Inc.
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