alpha2,3 sialic acid processing enzymes expression in gastric cancer tissues reveals that ST3Gal3 but not Neu3 are associated with Lauren's classification, angiolymphatic invasion and histological grade.

Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide. Despite progress in the last decades, there are still no reliable biomarkers for the diagnosis of and prognosis for GC. Aberrant sialylation is a widespread critical event in the development of GC. Neuraminidases (Neu) and sialyltransferases (STs) regulate the ablation and addition of sialic acid during glycoconjugates biosynthesis, and they are a considerable source of biomarkers in various cancers. This study retrospectively characterized Neu3 and ST3Gal3 expression by immunohistochemistry in 71 paraffin-embedded GC tissue specimens and analyzed the relationship between their expression and the clinicopathological parameters. Neu3 expression was markedly increased in GC tissues compared with non-tumoral tissues (p<0.0001). Intratumoral ST3Gal3 staining was significantly associated with intestinal subtype (p=0.0042) and was negatively associated with angiolymphatic invasion (p=0.0002) and higher histological grade G3 (p=0.0066). Multivariate analysis revealed that ST3Gal3 positivity is able to predict Lauren's classification. No associations were found between Neu3 staining and clinical parameters. The in silico analysis of mRNA expression in GC validation cohorts corroborates the significant ST3Gal3 association with higher histological grade observed in our study. These findings suggest that ST3Gal3 expression may be an indicator for aggressiveness of primary GC.

Synthesis and Anticancer Evaluation of Thiazacridine Derivatives Reveals New Selective Molecules to Hematopoietic Neoplastic Cells.

AIM AND OBJECTIVE: Cancer has become one of the leading causes of morbidity and mortality worldwide. Limitations associated with existing agents increase the need to develop more effective anticancer drugs to improve the therapeutic arsenal available. The aim of this study was to synthesize and evaluate the antiproliferative effects of three new thiazacridine derivatives. MATERIAL AND METHODS: Using a three steps synthesis reaction, three novel thiazacridine derivatives were obtained and characterized: (Z)-5-acridin-9-ylmethylene-3-(4-methyl-benzyl)-4-thioxo-thiazolidin- 2-one (LPSF/AC-99), (Z)-5-acridin-9-ylmethylene-3-(4-chloro-benzyl)-4-thioxo-thiazolidin-2- one (LPSF/AC-119) and (Z)-5-acridin-9-ylmethylene-3-(3-chloro-benzyl)-4-thioxo-thiazolidin-2- one (LPSF/AC-129). Toxicity and selectivity assays were performed by colorimetric assay. Then, changes in cell cycle and cell death induction mechanisms were assessed by flow cytometry. RESULTS: All compounds exhibited cytotoxicity to Raji (Burkitt's lymphoma) and Jurkat (acute T cell leukemia) cells, where LPSF/AC-119 showed best IC50 values (0.6 and 1.53 µ M, respectively). LPSF/AC-129 was the only cytotoxic compound in glioblastoma cell line NG97 (IC50 = 55.77 µ M). None of the compounds were toxic to normal human cells and induced neoplastic cell death primarily by apoptosis. CONCLUSION: All derivatives were more cytotoxic to hematopoietic neoplastic cells when compared to solid tumor derived cells. All three compounds are promising for in vivo and combination therapy studies against cancer.