Objective: To explore the roles of phosphorylated signal transduction and activator of transcription 3 (pSTAT3) and interleukin (IL)-17 expression of muscle in the disease activity of patients with idiopathic inflammatory myopathy (IIM). Methods: Twenty-eight patients with IIM (20 with dermatomyositis [DM] and 8 with anti-synthetase syndrome [ASS]) and 12 healthy controls (HCs) were enrolled in the study. The expression levels of p-STAT3 and IL-17 in muscle tissues were examined using Western blotting and immunohistochemical analyses. Results: The expressions of pSTAT3 were detected in atrophic and necrotic muscle cells around muscle fibers and in infiltrating inflammatory cells around blood vessels in DM patients and in mononuclear cells surrounding myocytes in ASS patients. The expressions of IL-17 were detected in muscle fibers and in infiltrating inflammatory cells around blood vessels in DM and ASS patients. However, they were not detected in the muscle tissue in HCs. Thus, the expression levels of p-STAT3 and IL-17 were significantly greater in the patients with IIM than in the HCs (P<0.05). Additionally, the p-STAT3 was positively correlated with the levels of IL-17in the muscle tissue ( r = 0.418, p = 0.027), IL-6 in the serum (r = 0.579, p = 0.001) , MYOACT score (r = 0.585, p = 0.001) , and the levels of AST (r =0.622, p < 0.001) , CK (r =0.714, p < 0.001) , LDH (r = 0.590, p = 0.001) , and HBD (r = 0.555, p = 0.003). Conclusion: The STAT3/IL-17 pathway is over-activated in patients with PM/ASS and plays a significant role in the disease activity.

Ornithine metabolism plays a vital role in tumorigenesis. For cancer cells, ornithine is mainly used as a substrate for ornithine decarboxylase (ODC) to produce amounts of polyamines. The ODC as a key enzyme of polyamine metabolism has become an important target for cancer diagnosis and treatment. To non-invasively detect the levels of ODC expression in malignant tumors, we have synthesized a novel 68 Ga-labeled ornithine analog ( 68 Ga-NOTA-Orn). The synthesis time of 68 Ga-NOTA-Orn was about 30 min with a radiochemical yield of 45-50% (uncorrected), and the radiochemical purity was > 98%. 68 Ga-NOTA-Orn was stable in saline and rat serum. Cellular uptake and competitive inhibition assays using DU145 and AR42J cells demonstrated that the transport pathway of 68 Ga-NOTA-Orn was similar to that of Lornithine, and it could interact with the ODC after transporting into the cell. Biodistribution and micropositron emission tomography (Micro-PET) imaging studies showed that 68 Ga-NOTA-Orn exhibited rapid tumor uptake and was rapidly excreted through the urinary system. All above results suggested that 68 Ga-NOTA-Orn is a novel amino acid metabolic imaging agent with great potential of tumor diagnosis.

No abstract

Ornithine metabolism plays a vital role in tumorigenesis. For cancer cells, ornithine is mainly used as a substrate for ornithine decarboxylase (ODC) to produce amounts of polyamines. The ODC as a key enzyme of polyamine metabolism has become an important target for cancer diagnosis and treatment. To non-invasively detect the levels of ODC expression in malignant tumors, we have synthesized a novel 68Ga-labeled ornithine analog (68Ga-NOTA-Orn). The synthesis time of 68Ga-NOTA-Orn was about 30 min with a radiochemical yield of 45–50% (uncorrected), and the radiochemical purity was > 98%. 68Ga-NOTA-Orn was stable in saline and rat serum. Cellular uptake and competitive inhibition assays using DU145 and AR42J cells demonstrated that the transport pathway of 68Ga-NOTA-Orn was similar to that of L-ornithine, and it could interact with the ODC after transporting into the cell. Biodistribution and micro-positron emission tomography (Micro-PET) imaging studies showed that 68Ga-NOTA-Orn exhibited rapid tumor uptake and was rapidly excreted through the urinary system. All above results suggested that 68Ga-NOTA-Orn is a novel amino acid metabolic imaging agent with great potential of tumor diagnosis.

No abstract