[Clinical prognosis analysis of patients with "double hit" multiple myeloma].

Objective: To analyze and explore the clinical characteristics and prognosis of patients with "double hit" multiple myeloma (MM) . Methods: We retrospectively analyzed 89 MM patients in our department of Shanghai Changzheng Hospital from 2010-2016. All patients were assayed by fluorescence in situ hybridization (FISH) and TP53 gene sequencing, based on Dr. Walker BA proposed the "double hit" MM concept, and then the clinical features and prognosis were evaluated. Results: In the results, 15 (16.85%) cases harbored "double hit" showed the median PFS of 8.4 months and the median OS 22.2 months, which was significantly lower than non-"double hit" patients with median PFS 14.2 months and the median OS 39.2 months, respectively (P<0.05) . Multivariate analysis displayed that the "double hit" was an independent poor prognostic factor on PFS (HR=2.171, 95%CI 1.206-3.907, P=0.010) and OS (HR=4.106, 95%CI 2.116-7.969, P<0.001) . Moreover, "double hit" MM patients had the higher adverse prognosis risk, which showed the shorter median OS and PFS than stage III of R-ISS patients (PFS 8.4 vs 11.8 months; OS 22.2 vs 24.3 months, P<0.05, respectively) . Conclusion: Patients with "double hit" MM have a very poor clinical prognosis. Prospective clinical studies are urgently needed to improve these extra high risk patients.

[Effect of Kruppel-like factor 2 on the migration of human liver sinusoidal endothelial cells].

Objective: To investigate the effect and mechanism of Kruppel-like factor 2 (KLF2) on the migration of human liver sinusoidal endothelial cells (LSEC). Methods: Cultured human LSEC were infected with different lenti-viruses to overexpress or suppress KLF2 expression (LV5-KLF2 and LV3-shKLF2, respectively), the infection efficacies were examined by real-time PCR and Western blot analysis.Transwell migration assay was used to investigate the role of KLF2 on the migration of LSEC.The mRNA and protein expression of vascular endothelial growth factor receptor-2 (VEGFR-2) were detected by real-time PCR and Western blot analysis, respectively.The expression and phosphorylation of Src, P38 MAPK, and P44/42 MAPK were detected by Western blot. Results: The up-regulation of KLF2 expression dramatically inhibited migration of treated LSEC, compared with LV5-NC and WT control cells, fewer LV5-KLF2 cells migrated to the lower side of the filter after 12 h [ (35.6±1.4), (71.3±2.4) and (69.3±1.6), P<0.001 for all comparisons]. In contrast, the down-regulation of KLF2 expression promoted the migration of LSEC, more LV3-KLF2 cells migrated to the lower side of the filter compared with the LV3-NC and WT control cells [(189.5±5.4), (83.4±2.5) and (82.2±3.4), P<0.001 for all comparisons]. Furthermore, up-regulation of KLF2 reduced the mRNA and protein expression level of VEGFR2, while down-regulation of KLF2 significantly increased its expression in LSEC.Additionally, up-regulation of KLF2 inhibited the phosphorylation of Src, P38 MAPK, and P44/42 MAPK pathway in LSEC, whereas down-regulation of KLF2 promoted the phosphorylation of those signaling pathway proteins. Conclusions: KLF2 may inhibit the migration of human LSEC through the Src/ MAPK signaling pathway.

High FoxP3 expression in tumour cells predicts better survival in gastric cancer and its role in tumour microenvironment.

BACKGROUND: Forkhead Box P3 (FoxP3) is thought to be a key transcription factor in regulatory T cells (Tregs), and recent data indicate that it is expressed in several tumour cells. However, its precise roles in gastric cancer (GC) and the underlying mechanisms regulating the interaction between GC cells and lymphocytes remain unclear. METHODS: FoxP3 expression was examined in tumour cells and Tregs in 150 cases of gastric precancer and cancer, and their prognostic significances were evaluated, respectively, using a tissue microarray containing 135 GC patient samples with a mean 102-month follow-up. FoxP3 involvement in the tumour cells-lymphocytes interaction and its gene function were further investigated. RESULTS: strong cytoplasmic staining of FoxP3 was observed in GC cells. FoxP3 protein expression in tumour cells predicts a good prognosis, whereas high-density Treg predicts a poor prognosis. Moreover, FoxP3 expression in GC cells increased after coculture with peripheral blood mononuclear cells through coculture systems. Upregulation of FoxP3 inhibited tumour growth in tumour-bearing nude mice. CONCLUSIONS: High FoxP3 expression in tumour cells predicts better survival in GC, possibility in relation to interaction between tumour cells and lymphocytes in microenvironment. Interfering with FoxP3 expression may open a new therapeutic strategy against tumour progression.