The influence of stacking fault energy on plasticity mechanisms in triode-plasma nitrided austenitic stainless steels: implications for the structure and stability of nitrogen-expanded austenite.
Alpha-B crystallin (CRYAB), as a small heat shock protein, has been found to be highly expressed in various human cancers and significantly associated with the unfavorable prognosis of these tumor. Nevertheless, the clinical significance of CRYAB in gastric cancer (GC) angiogenesis remains to be elucidated. In this study, we evaluated the expression of CRYAB and CD34 in GC tissues and corresponding normal gastric specimens to explore whether high level CRYAB is related with the angiogenesis and the poor prognosis in GC.In this study, the expression of CRYAB and CD34 were detected in GC tissues and corresponding normal gastric tissues by immunohistochemical (IHC) technique. Furthermore, the relationship of CRYAB with CD34-evaluated microvessel density (MVD) and poor prognosis was also investigated.CRYAB expression level was significantly higher in GC tissue than in normal gastric mucosa tissue, and clearly mean higher MVD was observed in tumor tissues compared with non-cancerous tissues. Besides, higher MVD value was observed in positive CRYAB expression group than in negative CRYAB expression group. Statistical analysis showed that CRYAB and MVD are associated with clinicopathological features including lymph node metastasis (LNM), tumor differentiation, invasion depth, and TNM stages. Kaplan-Meier method and multivariate survival analysis indicated that high expression of CRYAB, MVD, invasion depth, TNM stages, and tumor differentiation, as well as LNM significantly correlate with poor prognosis of GC patients.High expression of CRYAB may contribute to angiogenesis, invasion and metastasis of GC. These results indicated that CRYAB was expected to be a promising molecular marker for poor prognosis and potential therapeutic target in patients with GC.
Background: Disruptor of telomeric silencing-1-like (DOT1L), a methyltransferase of H3K79, was observed to be amplified and overexpressed in certain malignancies. This work was aimed at investigating the differences in DOT1L expression and its regulatory mechanism in gastric cancer (GC) and healthy samples. Methods: Immunohistochemistry was used to detect DOT1L levels in 101 cases of GC and marching adjacent normal tissues. DOT1L was inhibited by small interfering RNA (siRNA) and EPZ5676; a targeting drug. The ability of cells to proliferate were checked by cell counting kit-8 (CCK-8) and clone formation assays, with flow cytometry for observing the cell cycle. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot revealed the gene and protein profiles. Finally, the outcome of EPZ5676 administration was checked on a murine model. Results: The expression of DOT1L is significantly increased in gastric malignant tumors that is related to the degree of differentiation, lymph node metastasis and TNM staging. DOT1L serves as an independent marker for the prognosis of overall survival (OS) with high levels implying worse prognosis. In addition, DOT1L regulates cyclin-dependent kinase (CDK) 4 (CDK4) and CDK6 through H3K79me2, which leads to a change in the cell cycle at G 1 , thereby affecting the proliferation of tumors in vitro and in vivo. Conclusions: This is a first clinical demonstration of the applicability of DOT1L overexpression in gastric tumors. The work is suggestive of altered proliferation of cells by DOT1L via regulating cyclins and H3K79 methylation. This indicates the role of DOT1L in the prognosis and possible medical intervention of GC.
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