IL-8 –251A/T polymorphism is associated with decreased cancer risk among population-based studies: Evidence from a meta-analysis

Growing evidence suggests that interleukin-8 (IL-8) play pivotal roles in the pathogenesis of cancer through the modulation of tumour immune response or enhanced angiogenesis. A single nucleotide polymorphism, –251A/T, has been identified in the promoter region of the IL-8 gene and has been shown to influence its production. Results from previous studies on the association of –251A/T polymorphism with different cancer types remained contradictory. To assess the effect of –251A/T of IL-8 on cancer susceptibility, we conducted a meta-analysis, up to May 2009, of 14,876 cases with different cancer types and 18,465 controls from 45 published case–control studies. Summary odds ratios and corresponding 95% confidence intervals (CIs) for IL-8 polymorphism and cancer were estimated using fixed- and random-effects models when appropriate. The AA/AT genotypes were associated with a significantly increased risk of nasopharyngeal carcinoma when compared with TT genotype (OR = 1.48; 95% CI, 1.16–1.89). Moreover, significantly elevated risks were observed in ‘other cancers’, and also in African population when population is concerned. Interestingly, when stratified separately by population-based studies and hospital-based studies, significantly elevated risk was found among hospital-based studies (OR = 1.21, 95% CI, 1.07–1.37), whereas significantly decreased risk was found among population-based studies (OR = 0.90, 95% CI, 0.83–0.97). This meta-analysis shows that IL-8 –251A/T polymorphism may play a complex role in cancer development.     

Analysis of Efficacy and Prognostic Factors of Lenalidomide Treatment as Part of a Dutch Compassionate Use Program

Background and Methods:To obtain efficacy and safety data on lenalidomide treatment outside of clinical trials, we analyzed the clinical data of 114 patients with refractory or relapsed multiple myeloma treated with lenalidomide on a compassionate use basis. The recommended treatment consisted of lenalidomide 25 mg given on days 1-21 of a 28-day cycle, in combination with dexamethasone. A median of 3 previous lines of therapy were given, including thalidomide in 91%. Most patients were treated until progression or intolerable toxicity.Results:The median number of cycles was 7 (range, 1-21+ cycles) with a maximum response after a median of 3 cycles (range, 1-10 cycles). The overall response rate was 69%, including complete response in 6%, very good partial response in 19%, and partial response in 44%. The response rate was not influenced by previous thalidomide and/or bortezomib treatment. The median time to progression (TTP) was 9 months and the median overall survival (OS) was 22 months. A significantly longer TTP was observed in patients who previously underwent allogeneic stem cell transplantation (12.5 months vs. 8 months; P = .036). Overall survival was significantly affected by performance status (P < .0001). Lenalidomide toxicity was predominantly hematologic (37%; Common Toxicity Criteria ≥ 3) and the incidence of venous thrombotic events was low (5%) using the recommended prophylaxis.Conclusion:This analysis confirms that, outside clinical prospective trials, treatment with lenalidomide is highly effective and feasible in heavily pretreated patients with multiple myeloma.     

Evaluation of two different albumin depletion strategies for improved analysis of human CSF by SELDI-TOF-MS

ObjectivesTwo different depletion strategies for removing albumin from human cerebrospinal fluid (CSF), Microcon Centrifugal Filter vs. Montage Albumin Deplete kit, were evaluated for improving protein profiling pattern and reproducibility in SELDI analysis.Design and methodsPooled CSF was divided into 20 aliquots and these aliquots were subjected to SELDI analysis either after albumin depletion or without preprocessing. Protein profiles were obtained by using CM10, Q10 and IMAC chips.ResultsBoth strategies resulted in reliable albumin depletion (< 6.2 mg/L, filter; 8.1 mg/L, depletion kit). Investigated methods of albumin depletion showed no significant differences in coefficients of variation (CVs) of peak intensities compared to unprocessed CSF on almost all chip types. Peak intensities were significantly higher after albumin depletion compared to CSF without preprocessing on Q10 and on CM10 chips. Nevertheless, the two strategies of albumin depletion led to a decrease in the number of detected peaks on all chip types compared to unprocessed CSF, but several additional peaks, not detected in unprocessed CSF, occurred.ConclusionsThis study demonstrates that reduction of sample complexity by albumin depletion of CSF can be performed without CV impairment. However, the significance of this strategy needs to be evaluated separately for each individual biomarker discovery study.