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- Lapointe, Jacques, et al.
(författare)
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Gene expression profiling identifies clinically relevant subtypes of prostate cancer
- 2004
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 101:3, s. 811-816
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer, a leading cause of cancer death, displays a broad range of clinical behavior from relatively indolent to aggressive metastatic disease. To explore potential molecular variation underlying this clinical heterogeneity, we profiled gene expression in 62 primary prostate tumors, as well as 41 normal prostate specimens and nine lymph node metastases, using cDNA microarrays containing ≈26,000 genes. Unsupervised hierarchical clustering readily distinguished tumors from normal samples, and further identified three subclasses of prostate tumors based on distinct patterns of gene expression. High-grade and advanced stage tumors, as well as tumors associated with recurrence, were disproportionately represented among two of the three subtypes, one of which also included most lymph node metastases. To further characterize the clinical relevance of tumor subtypes, we evaluated as surrogate markers two genes differentially expressed among tumor subgroups by using immunohistochemistry on tissue microarrays representing an independent set of 225 prostate tumors. Positive staining for MUC1, a gene highly expressed in the subgroups with "aggressive" clinicopathological features, was associated with an elevated risk of recurrence (P = 0.003), whereas strong staining for AZGP1, a gene highly expressed in the other subgroup, was associated with a decreased risk of recurrence (P = 0.0008). In multivariate analysis, MUC1 and AZGP1 staining were strong predictors of tumor recurrence independent of tumor grade, stage, and preoperative prostate-specific antigen levels. Our results suggest that prostate tumors can be usefully classified according to their gene expression patterns, and these tumor subtypes may provide a basis for improved prognostication and treatment stratification.
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| 2. |
- Sharma, Sonia, et al.
(författare)
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Incident injury is strongly associated with subsequent incident temporomandibular disorder : results from the OPPERA study.
- 2019
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Ingår i: Pain. - : Lippincott Williams & Wilkins Ltd.. - 0304-3959 .- 1872-6623. ; 160:7, s. 1551-1561
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Tidskriftsartikel (refereegranskat)abstract
- Cross-sectional studies confirm, as expected, a positive association between jaw injury and painful temporomandibular disorders (TMDs), but prospective evaluations are lacking. We prospectively assessed incident jaw injury, injury type, and development of TMD in adults aged 18 to 44 years. Data were collected from 3258 individuals from communities surrounding 4 US academic institutes between 2006 and 2008. At enrollment, participants reported no TMD history and no facial injuries in the previous 6 months. Quarterly, follow-up questionnaires assessed incident jaw injury, which was classified as intrinsic (attributed to yawning or prolonged mouth opening) or extrinsic (attributed to other causes). Examiners classified incident TMD during a median follow-up period of 2.8 years (range 0.2-5.2 years). Cox regression models used jaw injury as a time-dependent covariate to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association with incident TMD. Among 1729 participants with complete data, 175 developed TMD. Eighty percent of injuries were intrinsic. Temporomandibular disorder annual incidence was nearly twice as high in those experiencing jaw injury (5.37%) compared with those who did not (3.44%). In the Cox model that accounted for timing of injury, the corresponding HR was 3.94 (95% CI = 2.82-5.50) after adjusting for study site, age, race, and sex. Hazard ratios did not differ (P = 0.91) for extrinsic injuries (HR = 4.03, 95% CI = 2.00-8.12) and intrinsic injuries (HR = 3.85, 95% CI = 2.70-5.49). Jaw injury was strongly associated with incident TMD. If surveillance and intervention after jaw injury is to be effective in preventing TMD, they should focus on both intrinsic and extrinsic injuries.
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