| 1. |
- Brennan, Donal J, et al.
(författare)
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Altered cytoplasmic-to-nuclear ratio of survivin is a prognostic indicator in breast cancer
- 2008
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 14:9, s. 2681-2689
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Survivin (BIRC5) is a promising tumor biomarker. Conflicting data exist on its prognostic effect in breast cancer. These data may at least be partly due to the manual interpretation of immunohistochemical staining, especially as survivin can be located in both the nucleus and cytoplasm. Quantitative determination of survivin expression using image analysis offers the opportunity to develop alternative scoring models for survivin immunohistochemistry. Here, we present such a model. Experimental Design: A breast cancer tissue microarray containing 102 tumors was stained with an anti-survivin antibody. Whole-slide scanning was used to capture high-resolution images. These images were analyzed using automated algorithms to quantify the staining. Results: Increased nuclear, but not cytoplasmic, survivin was associated with a reduced overall survival (OS; P = 0.038) and disease-specific survival (P = 0.0015). A high cytoplasmicto-nuclear ratio (CNR) of survivin was associated with improved OS (P = 0.005) and disease-specific survival (P = 0.05). Multivariate analysis revealed that the survivin CNR was an independent predictor of CIS (hazard ratio, 0.09; 95% confidence interval, 0.01-0.76; P = 0.027). A survivin CNR of >5 correlated positively with estrogen receptor (P = 0.019) and progesterone receptor (P = 0.033) levels, whereas it was negatively associated with Ki-67 expression (P = 0.04), p53 status (P = 0.005), and c-myc amplification (P = 0.016). Conclusion: Different prognostic information is supplied by nuclear and cytoplasmic survivin in breast cancer. Nuclear survivin is a poor prognostic marker in breast cancer. Moreover, CNR of survivin, as determined by image analysis, is an independent prognostic factor.
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| 2. |
- Brennan, Donal J., et al.
(författare)
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CA IX is an independent prognostic marker in premenopausal breast cancer patients with one to three positive lymph nodes and a putative marker of radiation resistance
- 2006
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 12:21, s. 6421-6431
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Hypoxia in breast cancer is associated with poor prognosis and down-regulation of the estrogen receptor. Carbonic anhydrase IX (CA IX) is a hypoxia-inducible gene that has been associated with poor outcome in many epithelial cancers. Previous studies of CA IX in breast cancer have been carried out on mixed cohorts of premenopausal and postmenopausal patients with locally advanced disease and varying treatment regimens. We examined the potential prognostic and predictive role of CA IX in premenopausal breast cancer patients. Experimental Design: Using tissue microarrays, we analyzed CA IX expression in 400 stage 11 breast cancers from premenopausal women. The patients had previously participated in a randomized control trial comparing 2 years of tamoxifen to no systemic adjuvant treatment. Median follow-up was 13.9 years. Results: CA IX expression correlated positively with tumor size, grade, hypoxia-inducible factor 1 alpha Ki-67, cyclin E, and cyclin A2 expression. CA IX expression correlated negatively with cyclin D1, estrogen receptor, and progesterone receptor. CA IX expression was associated with a reduced relapse-free survival (P = 0.032), overall survival (P = 0.022), and breast cancer specific survival (P = 0.005). Multivariate analysis revealed that CA IX was an independent prognostic marker in untreated patients with one to three positive lymph nodes (hazard ratio, 3.2; 95% confidence interval, 1.15-9.13; P = 0.027). Conclusion: CA IX is marker of poor prognosis in premenopausal breast cancer patients and it is an independent predictor of survival in patients with one to three positive lymph nodes. As all these patients received locoregional radiation therapy, CA IX may be associated with resistance to radiotherapy.
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| 3. |
- Evans, William J, et al.
(författare)
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Effect of recombinant human growth hormone on exercise capacity in patients with HIV-associated wasting on HAART.
- 2005
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Ingår i: The AIDS reader. - 1053-0894. ; 15:6
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Tidskriftsartikel (refereegranskat)abstract
- Over 700 patients with HIV-associated wasting while receiving HAART were randomly assigned to double-blind treatment for 12 weeks with recombinant human growth hormone (rhGH) daily or on alternate days, or to placebo. Maximum exercise intensity increased by a median of 2.35kJ in the alternate-days group and 2.60 kJ in the daily group but decreased by 0.25kJ in the placebo group. The median difference between the daily and placebo groups was 2.85 kJ (P < .0001). These improvements suggest that rhGH treatment may enable patients with wasting to perform activities of daily living that would be exhausting without rhGH treatment.
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| 4. |
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| 5. |
- O'Brien, Sallyarm L., et al.
(författare)
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CENP-F expression is associated with poor prognosis and chromosomal instability in patients with primary breast cancer
- 2007
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 120:7, s. 1434-1443
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Tidskriftsartikel (refereegranskat)abstract
- DNA microarrays have the potential to classify tumors according to their transcriptome. Tissue microarrays (TMAs) facilitate the validation of biomarkers by offering a high-throughput approach to sample analysis. We reanalyzed a high profile breast cancer DNA microarray dataset containing 96 tumor samples using a powerful statistical approach, between group analyses. Among the genes we identified was centromere protein-F (CENP-F), a gene associated with poor prognosis. In a published follow-up breast cancer DNA microarray study, comprising 295 tumour samples, we found that CENP-F upregulation was significantly associated with worse overall survival (p < 0.001) and reduced metastasis-free survival (p < 0.001). To validate and expand upon these findings, we used 2 independent breast cancer patient cohorts represented on TMAs. CENP-F protein expression was evaluated by immunohistochemistry in 91 primary breast cancer samples from cohort I and 289 samples from cohort II. CENP-F correlated with markers of aggressive tumor behavior including ER negativity and high tumor grade. In cohort I, CENP-F was significantly associated with markers of CIN including cyclin E, increased telomerase activity, c-Myc amplification and aneuploidy. In cohort II CENP-F correlated with VEGFR2, phosphorylated Ets-2 and Ki67, and in multivariate analysis, was an independent predictor of worse breast cancer-specific survival (p = 0.036) and overall survival (p = 0.040). In conclusion, we identified CENP-F as a biomarker associated with poor outcome in breast cancer and showed several novel associations of biological significance. (c) 2007 Wiley-Liss, Inc.
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| 6. |
- Pontius, Joan U, et al.
(författare)
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Initial sequence and comparative analysis of the cat genome
- 2007
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 17:11, s. 1675-1689
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Tidskriftsartikel (refereegranskat)abstract
- The genome sequence (1.9-fold coverage) of an inbred Abyssinian domestic cat was assembled, mapped, and annotated with a comparative approach that involved cross-reference to annotated genome assemblies of six mammals (human, chimpanzee, mouse, rat, dog, and cow). The results resolved chromosomal positions for 663,480 contigs, 20,285 putative feline gene orthologs, and 133,499 conserved sequence blocks (CSBs). Additional annotated features include repetitive elements, endogenous retroviral sequences, nuclear mitochondrial (numt) sequences, micro-RNAs, and evolutionary breakpoints that suggest historic balancing of translocation and inversion incidences in distinct mammalian lineages. Large numbers of single nucleotide polymorphisms (SNPs), deletion insertion polymorphisms (DIPs), and short tandem repeats (STRs), suitable for linkage or association studies were characterized in the context of long stretches of chromosome homozygosity. In spite of the light coverage capturing approximately 65% of euchromatin sequence from the cat genome, these comparative insights shed new light on the tempo and mode of gene/genome evolution in mammals, promise several research applications for the cat, and also illustrate that a comparative approach using more deeply covered mammals provides an informative, preliminary annotation of a light (1.9-fold) coverage mammal genome sequence.
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