Intratumoral and peritumoral radiomics analysis for preoperative Lauren classification in gastric cancer.

BACKGROUND: Preoperative prediction of the Lauren classification in gastric cancer (GC) is very important to the choice of therapy, the evaluation of prognosis, and the improvement of quality of life. However, there is not yet radiomics analysis concerning the prediction of Lauren classification straightly. In this study, a radiomic nomogram was developed to preoperatively differentiate Lauren diffuse type from intestinal type in GC. METHODS: A total of 539 GC patients were enrolled in this study and later randomly allocated to two cohorts at a 7:3 ratio for training and validation. Two sets of radiomic features were derived from tumor regions and peritumor regions on venous phase computed tomography (CT) images, respectively. With the least absolute shrinkage and selection operator logistic regression, a combined radiomic signature was constructed. Also, a tumor-based model and a peripheral ring-based model were built for comparison. Afterwards, a radiomic nomogram integrating the combined radiomic signature and clinical characteristics was developed. All the models were evaluated regarding classification ability and clinical usefulness. RESULTS: The combined radiomic signature achieved an area under receiver operating characteristic curve (AUC) of 0.715 (95% confidence interval [CI], 0.663-0.767) in the training cohort and 0.714 (95% CI, 0.636-0.792) in the validation cohort. The radiomic nomogram incorporating the combined radiomic signature, age, CT T stage, and CT N stage outperformed the other models with a training AUC of 0.745 (95% CI, 0.696-0.795) and a validation AUC of 0.758 (95% CI, 0.685-0.831). The significantly improved sensitivity of radiomic nomogram (0.765 and 0.793) indicated better identification of diffuse type GC patients. Further, calibration curves and decision curves demonstrated its great model fitness and clinical usefulness. CONCLUSIONS: The radiomic nomogram involving the combined radiomic signature and clinical characteristics holds potential in differentiating Lauren diffuse type from intestinal type for reasonable clinical treatment strategy.

Detection of human breast cancer cells using a 2-deoxy-D-glucose-functionalized superparamagnetic iron oxide nanoparticles.

BACKGROUND: Breast cancer is one of the most common type of female cancer worldwide and represents 14% of cancer-related deaths in women. Early detection is the most important factor for treatment and prognosis of breast cancer. In most countries, the women are currently screened with mammography only. Even though there has been considerable progress in the detection, surgical therapy, hormonal and target therapy of breast cancer, there are about ∼ 3500 000 women who die from breast cancer each year. Therefore, there is an urgent need to explore the new techniques for early detection of breast cancer. Magnetic resonance imaging (MRI) has the potential to improve breast cancer detection at an early stage because of its higher sensitivity. Glucose transporter (Glut) is a cellular transmembrane receptor that plays key roles in cell glucose metabolism and over-expressed in breast cancer cells. 2-deoxy-D-glucose having a similar structure to D-glucose can specifically interact with Glut. METHODS: In the present study, we constructed a 2-deoxy-D-glucose-functionalized superparamagnetic iron oxide (SPIO) nanoparticles that coated with meso-2,3-dimercaptosuccinic acid (γ-Fe2O3@DMSA-DG NPs). The aim of this study is to evaluate the efficacy of new constructed MRI contrast agent (γ-Fe2O3@DMSA-DG NPs) in detecting human breast cancers. RESULTS: Our results showed that breast cancer cells MDA-MD-231, MCF7 and ZR-75-1 had a high uptake rate of γ-Fe2O3@DMSA-DG NPs than human breast fibroblast cell HUM-CELL-0056. There was a significant difference of T2 relaxation times and signal intensity between breast cancer cells and human breast fibroblast cells labeled with γ-Fe2O3@DMSA-DG NPs when MIR. CONCLUSION: Our results indicated that γ-Fe2O3@DMSA-DG NPs may be used as a new MRI contrast agent for detection of breast cancer.

MRI of High-Glucose Metabolism Tumors: a Study in Cells and Mice with 2-DG-Modified Superparamagnetic Iron Oxide Nanoparticles.

PURPOSE: This study aims to evaluate the effect of dimercaptosuccinic acid (DMSA)-coated superparamagnetic iron oxide (γ-Fe(2)O(3)@DMSA) bearing the 2-deoxy-D-glucose (2-DG) ligand on targeting tumors with high-glucose metabolism. PROCEDURES: γ-Fe(2)O(3)@DMSA and 2-DG-conjugated γ-Fe(2)O(3)@DMSA (γ-Fe(2)O(3)@DMSA-DG) were prepared. The glucose consumption of MDA-MB-231 and MCF-7 breast cancer cells and human mammary epithelial cells (HMEpiCs) was assessed. Cells were incubated with γ-Fe(2)O(3)@DMSA or γ-Fe(2)O(3)@DMSA-DG, and MDA-MB-231 cells which exhibited the highest glucose consumption were used in breast cancer xenografts. Tumor targeting was studied by magnetic resonance imaging and Prussian blue staining in vivo. RESULTS: Glucose consumption was highest in MDA-MB-231 and lowest in HMEpiCs. In vitro, there was significant uptake of γ-Fe(2)O(3)@DMSA-DG by MDA-MB-231 and MCF-7 cells within 2 h and this was inhibited by glucose. Uptake of γ-Fe(2)O(3)@DMSA-DG was significantly higher in MDA-MB-231 compared with MCF-7 cells, and there was no obvious uptake of γ-Fe(2)O(3)@DMSA in either cell line. In vivo, γ-Fe(2)O(3)@DMSA-DG could be detected in the liver and in tumors post-injection, while γ-Fe(2)O(3)@DMSA was nearly undetectable in tumors. CONCLUSIONS: 2-DG-coated γ-Fe(2)O(3)@DMSA improved tumor targeting of γ-Fe(2)O(3)@DMSA which can be assessed by magnetic resonance imaging.

[Comparison of the targeting properties of 2-deoxy-D-glucose-conjugated nanoparticles to breast cancer MDA-MB-231 cells and breast fibroblasts cells].

OBJECTIVE: To compare the differences in uptake of 2-deoxy-D-glucose (2-DG)-conjugated nanoparticles between breast carcinoma MDA-MB-231 cells with high metabolism and breast fibroblasts with normal metabolism, and investigate the feasibility of using the coated nanoparticles as a MRI-targeted contrast agent for highly metabolic carcinoma cells. METHODS: The γ-Fe2O3@DMSA-DG was prepared. The glucose metabolism level of both cell lines was determined. The targeting efficacy of γ-Fe2O3@DMSA-DG and γ-Fe2O3@DMSA NPs to breast carcinoma MDA-MB-231 cells and breast fibroblasts at 10 min, 30 min, 1 h and 2 h was measured with Prussian blue staining and UV colorimetric assay. MRI was performed to visualize the changes of T2WI signal intensity. RESULTS: Prussian blue staining showed more intracellular blue granules in the MDA-MB-231 cells of γ-Fe2O3@DMSA-DG NPs group than that in the γ-Fe2O3@DMSA NPs group, and the γ-Fe2O3@DMSA-DG uptake was greatly competed by free D-glucose. As revealed by UV colorimetric assay, MDA-MB-231 cells also showed that the cellular iron amount of γ-Fe2O3@DMSA-DG group was significantly higher than that of the γ-Fe2O3@DMSA group and γ-Fe2O3@DMSA-DG + D-glucose group, statistically with a significant difference between them. MRI showed that the signal intensity of γ-Fe2O3@DMSA-DG group was decrease significantly, the T2 signal intensity was decreased by 10.5%, 37.5%, 72.9%, 92.0% for 10 min, 30 min, 1 h and 2 h, respectively. In contrast, the signal intensity did not show obvious decrease in the γ-Fe2O3@DMSA-DG group, the T2 signal intensity was decreased by 8.5%, 11.4%, 32.0%, 76.7% for 10 min, 30 min, 1 h and 2 h, respectively. However, HUM-CELL-0056 cells did not produce apparent difference for positive staining in the γ-Fe2O3@DMSA-DG group, γ-Fe2O3@DMSA group and γ-Fe2O3@DMSA-DG+D-glucose group, and the signal intensity also did not produce apparent difference. CONCLUSIONS: γ-Fe2O3@DMSA-DG has good targeting ability to highly metabolic breast carcinoma (MDA-MB-231) cells. It is feasible to serve as a specific MRI-targeted contrast agent for highly metabolic carcinoma cells, and deserves further studies in vivo.

Targeting Glut1-overexpressing MDA-MB-231 cells with 2-deoxy-D-g1ucose modified SPIOs.

Glucose transporter (Glut), a cellular transmembrane receptor, plays a key role in cell glucose metabolism and is linked to a poor prognosis in various human cancers. In this study, we prepared γ-Fe(2)O(3) NPs coated with DMSA, in which modified with 2-DG, then γ-Fe(2)O(3)@DMSA-DG NPs was constructed. The specific interactions between Glut1-overexpressing tumor cells (MDA-MB-231) and γ-Fe(2)O(3)@DMSA-DG NPs were observed using Prussian blue staining and transmission electron microscope (TEM), and found that γ-Fe(2)O(3)@DMSA-DG NPs were absorbed targetedly by the cells. Furthermore, the capacity of transporting SPIOs into tumor cells using these γ-Fe(2)O(3)@DMSA-DG NPs was evaluated with a 1.5 T clinical magnetic resonance imaging (MRI) scanner. It was found that the acquired MRI T2 signal intensity of MDA-MB-231 cells that were treated with the γ-Fe(2)O(3)@DMSA-DG NPs decreased significantly, and it was inhibited by competition with antibody of Glut1. Our results suggest that γ-Fe(2)O(3)@DMSA-DG NPs are a useful targeting to Glut1-overexpressing tumor cells in vitro and that γ-Fe(2)O(3)@DMSA-DG NPs may serve as a MRI-targeted tumor agent for better tumor imaging.

Preparation, characterization of 2-deoxy-D-glucose functionalized dimercaptosuccinic acid-coated maghemite nanoparticles for targeting tumor cells.

PURPOSE: To report a modified preparation and to systematically study the structure, magnetic and other properties of γ-Fe(2)O(3)-DMSA-DG NPs (2-deoxy-D-glucose (2-DG) conjugated meso-2,3-dimercaptosuccinic acid coated γ-Fe(2)O(3) nanoparticles) and test its ability to improve Hela tumor cells targeting in vitro compared to the γ-Fe(2)O(3)-DMSA NPs. METHODS: The conjugation of 2-DG on the surface of γ-Fe(2)O(3)-DMSA NPs was performed by esterification reaction and characterized. Acute toxicity was evaluated using MTT assay. Cellular uptake was investigated by Prussian blue staining and UV colorimetric assay. RESULTS: DG was successfully functionalized onto the surface of γ-Fe(2)O(3)-DMSA NPs; binding efficiency was ~60%. The mean diameter of single core of γ-Fe(2)O(3)-DMSA-DG NPs was 10 nm. Particle size and polydispersity index of its aggregates were 156.2 nm and 0.162, respectively. 2-DG-conjugated nanoparticles caused little cytotoxic effects on Hela cells at the concentration range of 0-600 µg/mL. When 2-DG-conjuated and non-conjugated nanoparticles were incubated with Hela cells for 4, 8 and 12 h, the 2-DG-conjugated nanoparticle showed significant amount of uptake in cells compared to their non-targeted counterparts. CONCLUSION: γ-Fe(2)O(3)-DMSA-DG NPs could be developed as a tumor-targeted probe for cervical cancer imaging and therapy.

[Uptake of 2-NBDG by human breast cancer cells in vitro].

OBJECTIVE: The purpose of this study was to assess the feasibility of fluorescent 2-deoxyglucose analog, 2-[N-(7-nitrobenz-2-oxa-1, 3-diaxol-4-yl)amino]-2-deoxyglucose (2-NBDG), that could be taken up by breast cancer cells highly expressing glucose transporter 1 (GLUT-1). The purpose of this study was to clarify if a fluorescent 2-deoxyglucose analog, 2-[N-(7-nitrobenz-2-oxa-1, 3-diaxol-4-yl)amino]-2-deoxyglucose (2-NBDG), can be taken up by breast cancer cells highly expressing glucose transporter 1 (GLUT-1), and to assess whether it can be used as a targeting imaging agent. METHODS: The expressions of GLUT-1 mRNA and protein in breast cancer MDA-MB-231 cells were detected by RT-PCR and immunohistochemistry, respectively. The difference of GLUT-1 protein expression between breast cancer MDA-MB-231 cells and MCF-7 cells was compared by Western blot. Secondly, MDA-MB-231 cells which were grown in 6-well plates were incubated with 2-NBDG, and the result of 2-NBDG uptake was analyzed by fluorescence microscopy and flow cytometry. The difference of 2-NBDG absorption in MDA-MB-231 and MCF-7 cells was compared by flow cytometry. RESULTS: The results of RT-PCR and immunohistochemistry confirmed that MDA-MB-231 cells highly expressed GLUT-1. Furthermore, Western blot revealed that GLUT-1 expression of MDA-MB-231 cells (0.946 ± 0.007) was higher than that in the MCF-7 cells (0.833 ± 0.010). Fluorescence microscopic and flow cytometric analysis showed that 2-NBDG was uptaken rapidly by MDA-MB-231 cells. Addition of 50 mmol/L D-glucose to the media with 2-NBDG reduced its uptake by 46.0%. Moreover, flow cytometry indicated that the fluorescence intensity of MDA-MB-231 cells (25.10 ± 0.57) was higher than that of MCF-7 cells (10.12 ± 0.62) when incubated with 2-NBDG for 20 minutes. CONCLUSION: The preliminary data clearly demonstrate that 2-NBDG is taken up and accumulated in breast cancer cells that highly express GLUT-1, and may be used as an optical probe for glucose uptake in hypermetabolic malignant cells.