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| 2. |
- Benhamou, S, et al.
(författare)
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Meta- and pooled analyses of the effects of glutathione S-transferase M1 polymorphisms and smoking on lung cancer risk
- 2002
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Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 23:8, s. 1343-1350
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Tidskriftsartikel (refereegranskat)abstract
- Susceptibility to lung cancer may in part be attributable to inter-individual variability in metabolic activation or detoxification of tobacco carcinogens. The glutathione S-transferase M1 (GSTM1) genetic polymorphism has been extensively studied in this context; two recent meta-analyses of case-control studies suggested an association between GSTM1 deletion and lung cancer. At least 15 studies have been published after these overviews. We undertook a new meta-analysis to summarize the results of 43 published case-control studies including >18 000 individuals. A slight excess of risk of lung cancer for individuals with the GSTM1 null genotype was found (odds ratio (OR) = 1.17, 95% confidence interval (CI) 1.07-1.27). No evidence of publication bias was found (P = 0.4), however, it is not easy to estimate the extent of such bias and we cannot rule out some degree of publication bias in our results. A pooled analysis of the original data of about 9500 subjects involved in 21 case-control studies from the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens (GSEC) data set was performed to assess the role of GSTM1 genotype as a modifier of the effect of smoking on lung cancer risk with adequate power. Analyses revealed no evidence of increased risk of lung cancer among carriers of the GSTM1 null genotype (age-, gender- and center-adjusted OR = 1.08, 95% CI 0.98-1.18) and no evidence of interaction between GSTM1 genotype and either smoking status or cumulative tobacco consumption.
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| 3. |
- Ermann, Joerg, et al.
(författare)
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CD4+CD25+ T cells facilitate the induction of T cell anergy
- 2001
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Ingår i: Journal of Immunology. - Rockville Pike, Bethesda, MD : The American Association of Immunologists, Inc.. - 0022-1767 .- 1550-6606. ; 167:8, s. 4271-4275
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Tidskriftsartikel (refereegranskat)abstract
- T cell anergy is characterized by the inability of the T cell to produce IL-2 and proliferate. It is reversible by the addition of exogenous IL-2. A similar state of unresponsiveness is observed when the proliferative response of murine CD4+CD25- T cells is suppressed in vitro by coactivated CD4+CD25+ T cells. We have developed a suppression system that uses beads coated with anti-CD3 and anti-CD28 Abs as surrogate APCs to study the interaction of CD4+CD25+ and CD4+CD25- T cells in vitro. CD4+CD25+ T cell-induced suppression, in this model, was not abrogated by blocking the B7-CTLA-4 pathway. When the CD4+CD25- T cells were separated from the CD4+CD25+ suppressor cells after 24 h of coactivation by the Ab-coated beads, the CD4+CD25- T cells were unable to proliferate or to produce IL-2 upon restimulation. The induction of this anergic phenotype in the CD4+CD25- T cells correlated with the up-regulated expression of the gene related to anergy in lymphocytes (GRAIL), a novel anergy-related gene that acts as a negative regulator of IL-2 transcription. This system constitutes a novel mechanism of anergy induction in the presence of costimulation.
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| 4. |
- Ford, Caroline, et al.
(författare)
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Progression from normal breast pathology to breast cancer is associated with increasing prevalence of mouse mammary tumor virus-like sequences in men and women
- 2004
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Ingår i: Cancer Research. - 1538-7445. ; 64:14, s. 4755-4759
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Tidskriftsartikel (refereegranskat)abstract
- Mouse mammary tumor virus (MMTV)-like sequences have been found in up to 40% of breast cancer samples but in <2% of normal breast tissue samples from Australian women studied by our group. Screening of a larger and more diverse cohort of female breast cancer samples has now shown a correlation of MMTV-like sequences with the severity (grade) of breast cancer. Thirty-two percent (43 of 136) of female breast cancer samples were positive for MMTV-like sequences when screened using PCR. A significant gradient of MMTV positivity was observed with increasing severity of cancer from 23% of infiltrating ductal carcinoma (IDC) grade I tumors to 34% of IDC grade II tumors (P = 0.00034) and 38% of IDC grade III tumors (P = 0.00002). We also report for the first time the detection of MMTV-like sequences in 62% (8 of 13) of male breast cancer samples and 19% (10 of 52) of male gynecomastia samples screened. MMTV-like sequences were demonstrated in various premalignant breast lesions of females, including fibroadenoma (20%) and fibrocystic disease (28%) samples, at a significantly higher prevalence than that seen in normal breast tissue (1.8%; P = 0.00001). Study of a longitudinal cohort of female breast cancer patients indicated that MMTV was co-incident with tumor but was not present when tumor was absent on histology. These results support the association of MMTV-like sequences with development of breast tumors in men and women and suggest association of MMTV with increasing severity of cancer.
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| 6. |
- Sazio, Pier, et al.
(författare)
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A silicon structure for electrical characterisation of nanoscale elements
- 2001
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Ingår i: MRS Spring Meeting 16-20 April 2001. ; 679E, s. B2.3-
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Konferensbidrag (refereegranskat)abstract
- The problem of mass manufacturing electrode structures suitable for contacting nanoscaleelements lies primarily in the difficulty of fabricating a nanometre-scale gap between twoelectrodes in a well controlled, highly parallel manner. In ULSI circuit production, the gate andsubstrate in MOSFETs are routinely fabricated with a precise vertical spacing of 3 nm betweenthem. In this work, we have investigated a number of highly parallel methods for the generationof nanogaps, including reconfiguration of the ubiquitous MOS device structure. The silicondioxide layer that provides vertical separation and electrical insulation between two regions ofsilicon (the crystalline substrate and the poly-crystalline gate) gives a leakage current of1 nA P-2 at 1 V for an oxide thickness of 2 nm [1]. This will enable objects the size of singlemolecules that are held across this layer to be detected electrically if they provide currents on thenanoampere scale, assuming a parasitic area for leakage between gate and substrate of order1 µm 2 . In the future this kind of device has the potential to provide a bolt-on technology for thefabrication of ULSI circuits in which conventional CMOS devices are directly hybridised withfunctional nanoscale elements.
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