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Enhanced fucosyltransferase IV ( FUT4) expression correlates with increased tumor malignancy in many carcinomas. However, little is known about the regulation of FUT4 expression, and whether FUT4 expression is influenced by the methylation status of the FUT4 promoter is unclear. In this study, we demonstrated that FUT4 expression is negatively correlated with the methylation degree of a CpG island in the FUT4 promoter, suggesting that the methylation status of FUT4 promoter regulates the expression of FUT4. The results indicate that manipulating the methylation status of the FUT4 promoter to regulate FUT4 expression may be a novel approach in the treatment of malignant tumors. [ABSTRACT FROM AUTHOR]

Background: Triple negative breast cancer (TNBC) remains the most challenging breast cancer subtype so far. Specific therapeutic approaches have rarely achieved clinical improvements in treatment of TNBC patients and effective molecular biomarkers are largely unknown. Methods: We used paired TNBC samples and high throughput RNA sequencing to identify differentially expressed circRNAs. Sucrose gradient polysome fractionation assay, antibody and Mass spectra were used to validate active circRNA translation. The novel protein function was validated in vitro and in vivo by gain or loss of function assays. Mechanistic results were concluded by immunoprecipitation analyses and kinase activity assay. Results: Circular HER2 RNA (circ-HER2) encoded a novel protein, HER2–103. Unexpectedly, while HER2 mRNA and protein were barely detected, circ-HER2/HER2–103 was expressed in ~ 30% TNBC clinical samples. Circ-HER2/HER2–103 positive TNBC patients harbored worse overall prognosis than circ-HER2/HER2–103 negative patients. Knockdown circ-HER2 inhibited TNBC cells proliferation, invasion and tumorigenesis in vitro and in vivo, suggesting the critical role of circ-HER2/HER2–103 in TNBC tumorigenicity. Mechanistically, HER2–103 promoted homo/hetero dimerization of epidermal growth factor receptor (EGFR)/HER3, sustained AKT phosphorylation and downstream malignant phenotypes. Furthermore, HER2–103 shared most of the same amino acid sequences as HER2 CR1 domain which could be antagonized by Pertuzumab, a clinical used HER2 antibody. Pertuzumab markedly attenuated in vivo tumorigenicity of circ-HER2/HER2–103 expressing TNBC cells but showed no effects in circ-HER2/HER2–103 negative TNBC cells. Conclusion: Our results not only demonstrated that certain TNBCs were not truly 'HER2 negative' but also highlighted the clinical implications of Pertuzumab in circ-HER2/HER2–103 expressing TNBC patients. [ABSTRACT FROM AUTHOR]

Background: There are approximately five Zhengs reported in psoriatic patients. Systematic data collection and proper analysis for the classification of psoriasis have been lacking. This study aims to cluster the Zhengs in psoriatic patients based on the application of a checklist of traditional Chinese medicine (TCM) symptoms and signs followed by latent class analysis (LCA)., Methods: A cross-sectional study of 507 psoriatic patients aged above 10 years was performed in Yunnan Provincial Hospital of TCM and the First Affiliated Hospital of Kunming Medicine University from October 2010 to September 2011 using a TCM symptoms and signs checklist obtained from 16 TCM experts by the Delphi technique. LCA was applied to obtain the best fitted model for clustering of symptoms and signs that can be interpreted as underlying Zhengs of psoriasis., Results: The LCA identified three Zhengs: dampness-heat Zheng (35.1%); blood heat Zheng (34.7%); and yin deficiency and blood dryness Zheng (30.2%). The first Zheng was associated with winter, the second with male sex, old age, smoking, and drinking alcohol, and the third with outpatient status, which reflected a mild disease course., Conclusions: In this study, 507 psoriasis patients were clustered into three Zhengs, which had different associated factors.

Background: Psoriasis is a chronic inflammatory skin disease with a genetic basis. Its ill-defined causes make it difficult to diagnose. This study aims to develop a diagnostic checklist for psoriasis classification in the context of traditional Chinese medicine., Methods: A Delphi study was conducted with three rounds by a panel of 16 dermatology experts to develop a checklist for traditional Chinese medicine symptoms and signs of psoriasis. Dermatology experts in psoriasis research, nine in Yunnan and seven in Beijing, were selected as the expert panel. The initial list of symptoms and signs in psoriasis was developed by reviewing the literature retrieved from Chinese and English journals. Experts rated each item of the list on a 5-point Likert scale. The list was revised and re-evaluated in the same manner for a total of 3 rounds before it was finalized., Results: One hundred and thirty items were extracted from the literature review. After three rounds of expert ratings, 96 items were retained with eight domains: color, type and shape of skin lesion, physical expression, tongue and coating, pulse, associated factors, and living environment. Intraclass correlation coefficient and Kappa statistics indicated an inter-rater agreement in the final checklist., Conclusion: A checklist containing 96 items in 8 domains was developed for psoriasis diagnosis using traditional Chinese medicine symptoms and signs.