Diagnostic Value of ER, PR, FR and HER-2-Targeted Molecular Probes for Magnetic Resonance Imaging in Patients with Breast Cancer.

BACKGROUND/AIMS: Smart molecular probes are required in the application of Magnetic resonance imaging (MRI) for biochemical and clinical research. This study aims to investigate the diagnostic values of estrogen receptor (ER), progesterone receptor (PR), folate receptor (FR) and human epidermal growth factor receptor 2 (HER-2)-targeted molecular probes in the MRI diagnosis of breast cancer. METHODS: Initially, a total of 508 female breast cancer patients were selected for breast cancer subtype classification by immunohistochemistry. Subsequently, the tumor size, lymph node metastasis, and histological grade of different breast cancer subtypes were compared. Molecular probes of Ab-ER-USPIO, Ab-PR-USPIO, Ab-FR-USPIO and Ab-HER-2-USPIO were constructed and screened. The specific binding of molecular probes to breast cancer cells was detected both in vitro and in vivo by Prussian blue staining and MRI using T1 and T2 weighted images. Finally, in vivo toxicity of Ab-HER-2-USPIO was analyzed using hematoxylin and eosin staining. RESULTS: We identified the following subtypes of breast cancer: Luminal A (ER-positive, FR-positive, HER-2-negative), Luminal B (ER-positive, FR-positive, HER-2-positive), HER-2 overexpression (ER-negative, FR-negative, HER-2-positive), and triple-negative breast cancer (ER-negative, FR-negative, HER-2-negative). Featuring favorable in vitro biocompatibility and low in vivo toxicity, Ab-HER-2-USPIO can specifically bind to breast cancer cells BT47 and SKBR3, thus enhancing the quality of T1 weighted MRI images. CONCLUSION: The results indicate that HER-2-targeted MRI molecular probes may be used in the clinical diagnosis of breast cancer and facilitate the development of promising strategies for breast cancer treatments.

Biocompatible composite nanoparticles with large longitudinal relaxivity for targeted imaging and early diagnosis of cancer.

Early diagnosis of cancer greatly increases the chances of successful treatment by radical resection. The sensitivity of magnetic resonance imaging (MRI) techniques for detecting early stage tumors can be increased with the assistance of a positive MRI contrast agent. However, the traditional positive MRI contrast agents, such as Gd-chelates and Gd-based inorganic nanoparticles, are often limited by their cytotoxicity and low specificity. Here, we propose a new design of MRI contrast agent based on gadolinium oxide nanocrystals (GON) for targeted imaging and cancer early diagnosis with good biocompatibility. The GON were prepared using a polyol method and then encapsulated into albumin nanoparticles (AN), which were cross-linked with glutaraldehyde and found to exhibit bright and stable autofluorescence without conjugation to any fluorescent agent. After that, a target molecule, folic acid (FA), was conjugated onto the surface of the GON-loaded AN (GON-AN) to construct a GON-AN-FA composite. The as-prepared nanoparticles are biocompatible and stable in serum. The results of MRI relaxation studies show that the longitudinal relaxivities (r1) of GON-AN (11.6 mM-1 s-1) and GON-AN-FA (10.8 mM-1 s-1) are much larger than those of traditional positive MRI contrast agents, such as Magnevist (3.8 mM-1 s-1). The results of cell viability assays indicate that GON-AN and GON-AN-FA are almost non-cytotoxic. Furthermore, the specificities of GON-AN and GON-AN-FA were evaluated with two kinds of cancer cells which overexpress folate receptor alpha (FRα). The results reinforce that the autofluorescent GON-AN-FA is able to target cancer cells via recognition of the ligand FA and the receptor FRα. Therefore, our autofluorescent GON-AN-FA possessing a large longitudinal relaxivity and good biocompatibility represents a significant advance for the targeted imaging and early diagnosis of cancer.

Anti-tumor effects of dihydroartemisinin on human osteosarcoma.

Dihydroartemisinin (DHA) exhibits antitumor activity against a wide spectrum of cancer cells. However, whether DHA has anti-tumor effect on human osteosarcoma cells remains unknown. This study aims to investigate the anti-tumor activity of DHA and the underlying mechanisms in human osteosarcoma cell lines with different p53 mutation statuses. Four human osteosarcoma cell lines were treated with different concentrations of DHA. Then, cell proliferation was determined by the CCK-8 viability assay; apoptosis and cell cycle progression were evaluated by flow cytometry; protein expression was analyzed by western blot assay; and NF-kB activity was examined by luciferase assay. The results demonstrated that DHA treatment could inhibit the proliferation of four osteosarcoma cell lines in a dose-dependent manner. P53 wild-type osteosarcoma cells were more sensitive to DHA. Moreover, the percentage of apoptotic cell and cell arrest in G2/M phase was increased upon DHA treatment in a dose-dependent manner. Mechanistically, DHA activated caspase-3, caspase-8, and caspase-9; upregulated the expression of Bax, FAS, and cyclin D1; downregulated the expression of Bcl-2, Cdc25B, and cyclin B1; and inhibited the activity of NF-кB. In conclusion, DHA has significant anticancer effects against human osteosarcoma cells, which include induction of apoptosis and cell cycle arrest. The p53 gene may play a certain role in the DHA-induced human osteosarcoma apoptosis and cell cycle arrest. DHA is a novel anti-osteosarcoma drug candidate that merits further study.

Respiratory syncytial virus infection and risk of acute myocardial infarction.

INTRODUCTION: Increasing evidences have shown that pathogens may promote atherosclerosis and trigger acute myocardial infarction (AMI). There is no report on the association between respiratory syncytial virus (RSV) infection and AMI. The case-control study was used to assess the association of previous RSV infection and acute myocardial infarction. METHODS: AMI cases and non-AMI controls were recruited from patients at a large teaching hospital in Harbin, China, during October 1, 2005, to March 31, 2006, and October 1, 2006, to March 31, 2007. Questionnaire survey was conducted to collect information on demographic characteristics and heart disease risk factors. Fasting blood sample was obtained to measure immunoglobulin G antibodies to RSV, Cytomegalovirus, herpes simplex virus type-1 and type-2, adenovirus, Rubella virus, Chlamydia pneumoniae and Helicobacter pylori and to measure the level of cholesterol, fasting serum glucose, triglycerides and high-sensitivity C-reactive protein. RESULTS: AMI group had more smokers than controls (56.9% versus 18.0%) and were more likely to have positive immunoglobulin G antibodies to RSV (OR, 6.2; 95% CI, 3.5-10.7; P < 0.001). After adjustment for potential confounding variables, the association between RSV and AMI remained (adjusted odds ratio, 11.1; 95% confidence interval, 3.3-29.5). CONCLUSIONS: Our study supported the hypothesis that the previous RSV infection was associated with AMI. This indicates that prevention and proper treatment of RSV infection are of great clinical importance for the reduction of AMI risk.

[Expression of co-stimulatory molecules and role of interleukin 18 in peripheral lymphocytes of patients with idiopathic thrombocytopenic purpura].

The objective of study was to investigate the expressions of CD80, CD86 and its ligand CD28 on peripheral lymphocytes in patients with idiopathic thrombocytopenic purpura (ITP), to explore the effect of interleukin 18 (IL-18) and its clinical significance in ITP. The expressions of co-stimulatory molecules (CD80, CD86 and its ligand CD28) on peripheral lymphocytes from 34 ITP patients and 34 normal humans were detected by immunofluorescence and flow cytometry. The IL-18 in the plasma was detected by using enzyme linked immunosorbent assay (ELISA). The results showed that the expressions of CD80 and CD86 on peripheral lymphocytes from ITP patients were higher than that of the normal control (4.21 +/- 2.27%, 7.19 +/- 5.16% vs 2.34 +/- 0.87%, 4.08 +/- 1.96%) (P < 0.01); the concentration of IL-18 in plasma of ITP patients was (538.31 +/- 111.33) pg/ml, but the concentration of IL-18 in plasma of controls was (489.44 +/- 49.07) pg/ml. The level of IL-18 negatively correlated with the platelet counts in peripheral blood (r = -0.395, P < 0.05). It is concluded that the CD28/CD80 and CD28/CD86 costimulatory molecules are overexpressed, when the IL-18 level in ITP patients is obviously higher than that in normal controls. When ITP occurred, and the co-stimulatory molecules CD80 and CD86 are closely associated with ITP, it seems that IL-18 may play an important role in ITP pathogenesis.