Lung adenocarcinoma-related target gene prediction and drug repositioning.

Lung cancer is the leading cause of cancer deaths globally, and lung adenocarcinoma (LUAD) is the most common type of lung cancer. Gene dysregulation plays an essential role in the development of LUAD. Drug repositioning based on associations between drug target genes and LUAD target genes are useful to discover potential new drugs for the treatment of LUAD, while also reducing the monetary and time costs of new drug discovery and development. Here, we developed a pipeline based on machine learning to predict potential LUAD-related target genes through established graph attention networks (GATs). We then predicted potential drugs for the treatment of LUAD through gene coincidence-based and gene network distance-based methods. Using data from 535 LUAD tissue samples and 59 precancerous tissue samples from The Cancer Genome Atlas, 48,597 genes were identified and used for the prediction model building of the GAT. The GAT model achieved good predictive performance, with an area under the receiver operating characteristic curve of 0.90. 1,597 potential LUAD-related genes were identified from the GAT model. These LUAD-related genes were then used for drug repositioning. The gene overlap and network distance with the target genes were calculated for 3,070 drugs and 672 preclinical compounds approved by the US Food and Drug Administration. At which, bromoethylamine was predicted as a novel potential preclinical compound for the treatment of LUAD, and cimetidine and benzbromarone were predicted as potential therapeutic drugs for LUAD. The pipeline established in this study presents new approach for developing targeted therapies for LUAD.

[Safety, biodistribution, and dosimetry of myocardial imaging agent 99Tc(m)N-NOET in healthy volunteers].

OBJECTIVE: To study the safety, biodistribution, and dosimetry of myocardial perfusion imaging agent 99Tc(m)N-NOET in 10 healthy volunteers. METHODS: 744-792 MBq of 99Tc(m)N-NOET was injected to each volunteer. Safety parameters and adverse event was measured in 24 hours of injection. Biodistribution was studied by whole-body imaging 1, 30 minutes, 1, 2, 4, 8, and 24 hours after the injection of 99Tc(m)N-NOET. The estimation of dosimetry was based on the standard medical internal radiation dose method using MIRDOSE 3.0 analysis program. Myocardial single photon emission computed tomography (SPECT) imaging was performed at 1 and 4 hours after injection. RESULTS: No undesirable effects were reported by the subject during 24 hours after injection of 99Tc(m)N-NOET. No clinically significant changes were found in vital signs (heart rate, blood pressure, and electrocardiogram). No biochemical aspects and serology changes were measured. The myocardial SPECT imaging was clear. Cardiac uptake of 99Tc(m)N-NOET was as high as 2.68% at 2 hours after injection. The heart to lung ratio was more than 1 from 30 minutes after injection, reaching a maximum of 1.91 +/- 0.53 at 2 hours after injection. Radiation dosimetry calculations indicated an effective absorbed dose of 1.28 x 10(-5) Sv/MBq. The dosimetry in each main organ is lower then 50 mGy given 740 MBq of 99Tc(m)N-NOET in once imaging. CONCLUSIONS: 99Tc(m)N-NOET exhibits high cardiac uptake and low estimated effective absorbed dose. It's a safe myocardial perfusion imaging agent.

[Diagnosis of coronary artery disease with 99Tcm-N-NOET myocardial perfusion imaging].

OBJECTIVE: To evaluate the sensitivity and specificity of (99)Tc(m)-N-NOET myocardial perfusion tomographic imaging (MPI) for the diagnosis of coronary artery disease (CAD). METHODS: Coronary angiography and (99)Tc(m)-N-NOET myocardial perfusion tomographic imaging were performed in the patients hospitalized in the Department of Cardiology, Peking Union Medical College Hospital, from June to December 2005 with known or suspected diagnosis of CAD. Adenosine was infused intravenously at a rate of 140 microg x kg(-1)min(-1) for 6 minutes. At the third minute of adenosine infusion, 740 MBq (20 mCi) (99)Tc(m)-N-NOET was injected intravenously. MPI was obtained 15 minutes after the (99)Tc(m)-N-NOET infusion. If the result was abnormal, rest myocardial perfusion imaging would be performed 2 hours later. Coronary angiography was performed in all patients within one week after the myocardial perfusion imaging. RESULTS: Myocardial perfusion imaging was performed in 53 cases, 36 males and 17 females, aged 56 +/- 10, who underwent coronary angiography, among which 31 had > or = 50% stenosis of coronary artery and 23 had normal coronary artery. All of the patients with stenosis of coronary artery had positive (99)Tc(m)-N-NOET adenosine stress myocardial perfusion imaging. Nineteen out of the 29 cases without stenosis of coronary artery had negative adenosine myocardial perfusion imaging. The sensitivity and specificity of (99)Tc(m)-N-NOET adenosine myocardial perfusion imaging were 100% and 73% respectively in the detection of stenosis of coronary arteries. Seven cases got percutaneous coronary intervention and 2 got coronary artery bypass graft. Six of the 9 patients undergoing revascularization had stenosis of stents or grafts, 5 of which had positive myocardial perfusion imaging. 3 cases hadn't restenosis and their results of myocardial perfusion imaging were negative. CONCLUSION: (99)Tc(m)-N-NOET myocardial perfusion imaging is a useful non-interventional method for detecting coronary artery stenosis.

[Preliminary clinical application of 99Tcm-HYNIC-TOC imaging in somatostatin receptor-positive tumors].

OBJECTIVE: To evaluate the effect of 99Tcm-HYNIC-TOC imaging in localization of somatostatin receptor-positive tumors. METHODS: Forty-four patients were involved in this study, including 22 neuroendocrine tumors, 10 non-neuroendrocrine tumors and 12 benign diseases. All patients were confirmed by histopathologic diagnosis, and had clinical laboratory data, or 1-2 other imaging procedures. Regional, whole body and SPECT/CT (in positive cases) imagings were acquired at 1 and 4 hours after an intravenous injection of 370 MBq 99Tcm-HYNIC-TOC. 99Tcm-HYNIC-TOC imaging was compared with 111In-petetreotide imaging in 4 cases, and with 131I-MIBG imaging in 10 cases. 99Tcm-HYNIC-TOC imaging was performed before and after treatment in 1 non-Hodgkins lymphoma (NHL) patient. RESULTS: The positive imagings were observed in 19 of 32 cases. The sensitivity, specificity, and accuracy of 99Tcm-HYNIC-TOC imaging for somatostatin receptor-positive tumors are 82.6%, 100%, and 87.5%, respectively. The distribution in vivo of 99Tcm-HYNIC-TOC is similar to that of 111In-petetreotide, and showed high physiological uptake in liver, spleen, and kidneys. 99Tcm-HYNIC-TOC imaging demonstrated intense tumor sites uptake at 1 hour after injection, and revealed the lesions first in 6 patients among the imaging modalities, and more lesions that had not been revealed by 131I-MIBG imaging. Compared with imaging before treatment, 99Tcm-HYNIC-TOC imaging confirmed the tumor regression after treatment in 1NHL. CONCLUSIONS: 99Tcm-HYNIC-TOC is promising for the diagnosis and localization of somatostatin receptor-positive tumors.