L’hyperprolactinémie dans le syndrome de Gougerot-Sjögren est-elle une caractéristique d’un sous-groupe de patients ou fait-elle partie de la maladie ?

Objective. – To investigate the prevalence of hyperprolactinemia in patients with primary Sjogren’s syndrome (SS), its clinical significance and its implication to our understanding of the disease pathogenesis.Materials and methods. – Forty-nine patients with primary SS syndrome (44 females and 5 males) age range 37–66 years were included in this study. All patients underwent clinical assessment for disease manifestations in addition to the laboratory assessment for serum prolactin, sex hormones and immunological profile. Fifty healthy subjects (44 females and 6 males) of matched age were studied as control group.Results. – The mean prolactin serum level was significantly higher in SS patients compared to the control group (P < 0.01). This significant difference was persistent after subgrouping the patients and the controls based on their menstrual history. Hyperprolactinemia (>20 ng/ml) was prevalent in 16.3% of SS patients. There was no correlation between serum prolactin levels and hormonal status, auto-antibodies as well as systemic manifestations of the disease.Conclusion. – Patients with primary SS have moderately increased the levels of prolactin. Hyperprolactinemia reflects the disease pathology rather than being present in a subset of patients. The presence of elevated prolactin levels was not associated with hormonal status, clinical or immunological manifestations of primary SS.     

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.     

Development of a novel small antibody that retains specificity for tumor targeting

Background

For the targeted therapy of solid tumor mediated by monoclonal antibody (mAb), there have different models of rebuilding small antibodies originated from native ones. Almost all natural antibody molecules have the similar structure and conformation, but those rebuilt small antibodies cannot completely keep the original traits of parental antibodies, especially the reduced specificity, which gravely influences the efficacy of small antibodies.

Methods

In this study, authors developed a novel mimetic in the form of V_HFR1_C-10-V_HCDR1-V_HFR2-V_LCDR3-V_LFR4_N-10for a parental mAb induced with human breast cancer, and the mimetic moiety was conjugated to the C-terminal of toxicin colicin Ia. The novel fusion peptide, named protomimecin (PMN), was administered to MCF-7 breast cancer cells to demonstrate its killing competency in vitro and in vivo.

Results

Compared with original antibody-colicin Ia (Fab-Ia) and single-chain antibody-colicin Ia (Sc-Ia) fusion proteins, PMN retained the targeting specificity of parental antibody and could specifically kill MCF-7 cells in vitro. By injecting intraperitoneally into BALB/c athymic mice bearing MCF-7 tumors, with reduced affinity, PMN significantly suppressed the growth of tumors compared with control mice treated by toxicin protein, Fab-Ia protein, Sc-Ia protein or by PBS (p < 0.05).

Conclusion

This novel mimetic antibody retained original specificity of parental antibody, and could effectively guide killer moiety to suppress the growth of breast cancer by targeted cell death.