Elevated tumour interleukin-1β is associated with systemic inflammation: a marker of reduced survival in gastro-oesophageal cancer

Systemic inflammation is associated with adverse prognosis cancer but its aetiology remains unclear. We investigated the expression of proinflammatory cytokines within normal mucosa from healthy controls and tumour tissue in cancer patients and related these levels with markers of systemic inflammation and with the presence of a tumour inflammatory infiltrate. Tissue was collected from 56 patients with gastro-oesophageal cancer and from 12 healthy controls. Tissue cytokine mRNA concentrations were measured by real-time PCR and tissue protein concentrations by cytometric bead array. The degree of chronic inflammatory cell infiltrate was recorded. Serum cytokine and acute phase protein concentrations (including C-reactive protein (CRP)) were measured by enzyme-linked immunosorbent assay. Proinflammatory cytokines were significantly overexpressed (interleukin (IL)-1β, IL-6, IL-8 and tumour necrosis factor-α) both at mRNA and protein levels in the cancer specimens compared with mucosa from controls. Interleukin-1β was expressed in greatest (10–100-fold) concentration and protein levels correlated significantly with systemic inflammation (CRP) (P=0.05, r=0.31). A chronic inflammatory infiltrate was observed in 75% of the cancer specimens and was associated with systemic inflammation (CRP: P=0.01). However, the presence of chronic inflammation per se was not associated with altered cytokine expression within the tumour. Both a chronic inflammatory infiltrate and systemic inflammation (CRP) were associated with reduced survival (P=0.05 and P=0.03, respectively). Tumour chronic inflammatory infiltrate and tumour tissue IL-1β overexpression are potential independent factors influencing systemic inflammation in oesophagogastric cancer patients

A Meta-Analysis of Interleukin-8 -251 Promoter Polymorphism Associated with Gastric Cancer Risk

Background: Potential functional allele A/T single nucleotide polymorphism (SNP) of Interleukin 8 (IL-8) promoter-251has been implicated in gastric cancer risk. Methods: We aimed to explore the role of A/T SNP of IL-8-251 in the susceptibility to gastric cancer through a systematic review and meta-analysis. Each initially included article was scored for quality appraisal. Desirable data were extracted and registered into databases. Eighteen studies were ultimately eligible for the meta-analysis of IL-8- 251 A/T SNP. We adopted the most probably appropriate genetic model (codominant model). Potential sources of heterogeneity were sought out via stratification and sensitivity analyses, and publication biases were estimated. Results: Between IL-8-251 AA genotype with gastric cancer risk, statistically significant association could be noted with overall gastric cancer, evidently noted in Asians, witnessed in high quality subgroup, and apparently noted in intestinal-type gastric cancer. Conclusions: Our meta-analysis indicates that IL-8-251 AA genotype is associated with the overall risk of developing gastric cancer and may seem to be more susceptible to overall gastric cancer in Asian populations. IL-8-251 AA genotype is more associated with the intestinal-type gastric cancer. IL-8-251 AA genotype is not associated with Helicobacter Pylori infection status in our meta-analysis

Run Away or Stick Together? The Impact of Organization-Specific Adverse Events on Alliance Partner Defection

Alliances are inter-organizational relationships wherein partners agree to engage in joint action and share benefits and burdens. But when might an adverse event that strikes one partner become too burdensome for another partner? Extant theories of alliance instability provide incomplete answers, which is problematic: for stricken organizations, anticipating whether their non-stricken partners will remain in the alliance can be essential for survival. Integrating insights from alliance dynamics and organizational stigma literatures, we theorize how an organization-specific adverse event affects a non-stricken partner's decision to continue with or defect from an alliance by considering factors that shift the balance between cohesive and disruptive forces. We propose that high stigmatization risk will increase the probability of partner defection through two disruptive mechanisms: relational uncertainty and stigma anxiety. Building on the idea that the same factors contributing to alliance formation may also condition partner defection, we theorize about the roles of partner resource interdependencies, relational embeddedness, and perceived partner similarity in amplifying or attenuating disruptive mechanisms triggered by an adverse event. We extend the research on partner defection and alliance instability by advancing an event-based view of alliance instability and specifying the conditions under which an alliance partner might defect