3-aminopyridine-2-carboxaldehyde-thiosemicarbazone and Stomach-Neoplasms

In this paper, a series of thiosemicarbazone derivatives containing different aromatic heterocyclic groups were synthesized and the tridentate donor system of the lead compound was optimized. Most of the target compounds showed improved antiproliferative activity against MGC803 cells. SAR studies revealed that compound 5d displayed significant advantages in inhibition effect with an IC

Topics: Antineoplastic Agents; Apoptosis; Cell Cycle Checkpoints; Cell Proliferation; Dose-Response Relationship, Drug; Drug Discovery; Drug Screening Assays, Antitumor; Epithelial-Mesenchymal Transition; Humans; Molecular Structure; Stomach Neoplasms; Structure-Activity Relationship; Thiosemicarbazones; Tumor Cells, Cultured; Wound Healing

The purpose of this study was to evaluate baseline RRM2 protein and gene expression in tumors of patients receiving 3-AP.. Tumor blocks from patients enrolled in phase I and II clinical studies using 3-AP, were evaluated for RRM2 gene and protein expression by quantitative real time polymerase chain reaction (Q-RTPCR) and automated quantitative analysis (AQUA).. Esophageal and gastric cancers overexpressed RRM2 protein when compared to prostate cancer (Z-score, 0.68 +/- 0.94 SD, vs 0.41 +/- 0.84 SD, respectively; p = 0.04). Esophageal and gastric cancers also overexpressed RRM2 mRNA when compared to prostate cancer (relative gene expression 2.56 +/- 1.49 SD, vs 0.29 +/- 0.20 SD, respectively; p = 0.02). Protein and gene expression were moderately associated (Spearman's rank correlation = 0.30; p = 0.12).. RRM2 gene and protein expression varies by tumor type.

Topics: Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Esophageal Neoplasms; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Male; Polymerase Chain Reaction; Prostatic Neoplasms; Protein Subunits; Pyridines; Ribonucleoside Diphosphate Reductase; RNA, Messenger; Stomach Neoplasms; Thiosemicarbazones