Comparison of different images in gross target volume delineating on VX2 nasopharyngeal transplantation tumor models.

Background: To determine the optimum conditions for diagnosis of nasopharyngeal carcinoma, we established VX2 rabbit model to delineate gross target volume (GTV) in different imaging methods. Methods: The orthotopic nasopharyngeal carcinoma (NPC) was established in sixteen New Zealand rabbits. After 7-days inoculation, the rabbits were examined by CT scanning and then sacrificed for pathological examination. To achieve the best delineation, different GTVs of CT, MRI, 18F-FDG PET/CT, and 18F-FLT PET/CT images were correlated with pathological GTV (GTVp). Results: We found 45% and 60% of the maximum standardized uptake value (SUVmax) as the optimal SUV threshold for the target volume of NPC in 18F-FDG PET/CT and 18F-FLT PET/CT images, respectively (GTVFDG45% and GTVFLT60%). Moreover, the GTVMRI and GTVCT were significantly higher than the GTVp (P ≤ 0.05), while the GTVFDG45% and especially GTVFLT60% were similar to the GTVp (R = 0.892 and R = 0.902, respectively; P ≤ 0.001). Conclusions: Notably, the results suggested that 18F-FLT PET/CT could reflect the tumor boundaries more accurately than 18F-FDG PET/CT, MRI and CT, which makes 18F-FLT PET-CT more advantageous for the clinical delineation of the target volume in NPC.

In vitro and in vivo apatinib inhibits vasculogenic mimicry in melanoma MUM-2B cells.

The effect of apatinib on the formation of vasculogenic mimicry (VM) was studied in a malignant melanoma cell line. MUM-2B cells cultured in three-dimensional Matrigel were treated with varying concentrations (0, 0.01, 0.05, 0.1, 0.5 µmol/L) of apatinib to test its effect on VM in vitro, followed by MTT proliferation and transwell invasion assays to determine the effect of apatinib on cell proliferation and invasion of MUM-2B cells. In vivo, we used a melanoma cancer model to test the effect of short-term apatinib (100, 200, 300 mg/kg) treatment on VM. Western blotting, immunohistochemistry staining, and CD31-PAS dual staining were performed to assess the expression of VEGFR-2, ERK-1/2, PI3K, and MMP-2, and formation of VM. The results showed apatinib-treated groups formed a lesser number of VM in 3D matrigel, while the cell viability in MTT proliferation assay and the number of migration cells in transwell invasion assay were significantly lower in apatinib-treated groups. In addition, short-term apatinib treatment inhibited angiogenesis, VM formation, and tumor growth in models of melanoma cancer. Mice in apatinib-treated groups showed a markedly reduced expression of VEGFR-2, ERK-1/2, PI3K, and MMP-2. In summary, apatinib could inhibit the expression of VEGFR-2, and downregulate the ERK1/2/PI3K/MMP-2 signaling cascade, which may be one of the underlying mechanisms by which apatinib inhibits angiogenesis and the development of VM in models of melanoma cancer, and restrains the formation of VM by MUM-2B cells. Apatinib shows inhibitory effects on cell proliferation and invasion of MUM-2B cells, which is a close relationship with the VM.

In vivo antitumor effect of endostatin-loaded chitosan nanoparticles combined with paclitaxel on Lewis lung carcinoma.

The purpose of this study was to prepare endostatin-loaded chitosan nanoparticles (ES-NPs) and evaluate their antitumor effect when combined with paclitaxel (PTX) on Lewis lung carcinoma (LLC) mouse xenografts. ES-NPs were prepared by ionic cross-linking. Characterization of the ES-NPs included size distribution, drug-loading efficiency (DL), and encapsulation efficiency (EE). An in vitro release test was also used to determine the release behavior of the ES-NPs. A subcutaneous LC xenograft model of C57BL/6J mice was established. The mice were randomly divided into six groups: control (0.9% NaCl), ES, PTX, ES-NPs, ES + PTX, and ES-NPs + PTX. The tumor volume was dynamically measured for the duration of the experiment. Immunohistochemistry was performed to determine the Ki-67 and microvascular density (MVD) in each group. Serum vascular endothelial growth factor (VEGF) and ES levels were determined by enzyme-linked immunosorbent assay (ELISA). ES-NPs were successfully synthesized and had suitable size distribution and high EE. The NPs were homogenously spherical and exhibited an ideal release profile in vitro. In vivo, tumor growth was significantly inhibited in the ES-NPs + PTX group. The tumor inhibitory rate was significantly higher in the ES-NPs + PTX group than in the other groups (p < .05). The results of the immunohistochemical assay and ELISA confirmed that ES-NPs combined with PTX had a strong antiangiogenic effect. ES-NPs can overcome the shortcomings of free ES, such as short retention time in circulation, which enhances the antitumor effect of ES. The antitumor effect was more pronounced when treatment included PTX and ES-loaded NPs.

Lymph node tuberculosis mimicking malignancy on 18F-FDG PET/CT in two patients: A case report.

18F-fluorodeoxyglucose positron emission/computed tomography (18F-FDG PET/CT) imaging, an established procedure for evaluation of malignancy, reports an increased 18F-FDG uptake in acute or chronic inflammatory condition. Lymph node tuberculosis (LNTB) is the most common form of extrapulmonary tuberculosis. However, the absence of clinical symptoms and bacteriological basis makes it difficult to diagnose. In the current case report, two patients with LNTB mimicking malignant lymphoma are presented by 18F-FDG PET/CT. The objective of the present report is to emphasize that LNTB should be considered as a noteworthy differential diagnosis in patients with enlarged lymph nodes, particularly in tuberculosis-endemic countries, and that lymph node biopsy serves a vital role in diagnosing LNTB.

Danshensu, a major water-soluble component of Salvia miltiorrhiza, enhances the radioresponse for Lewis Lung Carcinoma xenografts in mice.

The molecule 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoic acid (danshensu), a herbal preparation used in traditional Chinese medicine, has been found to possess potential antitumor and anti-angiogenesis effects. The aim of the present study was to investigate the efficacy of the combination of radiation therapy (RT) with danshensu in the treatment of Lewis lung carcinoma (LLC) xenografts, whilst exploring and evaluating the mechanism involved. In total, 8-week old female C57BL/6J mice were randomly assigned into 3 groups to receive: RT, RT + cisplatin and RT + danshensu, respectively, when LLC reached 100-150 mm3. Each group was divided into 7 subgroups according to the different irradiation doses that were administered. Tumor growth curves were created and the sensitization enhancement ratios of the drugs were calculated. The experiment was then repeated, and the 4 groups of tumor-bearing mice were treated with natural saline, danshensu, RT + danshensu and RT, respectively. The mice were sacrificed on day 7, and tumor tissue and blood were collected to determine microvessel density, the expression of proangiogenic factors, and the levels of blood thromboxane B2 and 6-keto-prostaglandin-F1α. Tumor hypoxia was also detected using in vivo fluorescence imaging. With respect to LLC xenografts, treatment with danshensu + RT significantly enhanced the effects of tumor growth inhibition (P<0.05). Furthermore, tumor vasculature was remodeled and microcirculation was improved, which significantly reduced tumor hypoxia (P<0.05). The present study demonstrated that danshensu significantly enhanced the radioresponse of LLC xenografts in mice. The mechanism involved may be associated with the alleviation of tumor cell hypoxia following treatment with danshensu + RT, caused by the improvement of tumor microcirculation and the remodeling of tumor vasculature.

Preparation of endostatin-loaded chitosan nanoparticles and evaluation of the antitumor effect of such nanoparticles on the Lewis lung cancer model.

The purpose of this study was to prepare ES-loaded chitosan nanoparticles (ES-NPs) and evaluate the antitumor effect of these particles on the Lewis lung cancer model. ES-NPs were prepared by a simple ionic cross-linking method. The characterization of the ES-NPs, including size distribution, zeta potential, loading efficiency and encapsulation efficiency (EE), was performed. An in vitro release test was also used to determine the release behavior of the ES-NPs. Cell viability and cell migration were assayed to detect the in vitro antiangiogenic effect of ES-NPs. In order to clarify the antitumor effect of ES-NPs in vivo, the Lewis lung cancer model was used. ES-NPs were successfully synthesized and shown to have a suitable size distribution and high EE. The nanoparticles were spherical and homogeneous in shape and exhibited an ideal releasing profile in vitro. Moreover, ES-NPs significantly inhibited the proliferation and migration of human umbilical vascular endothelial cells (HUVECs). The in vivo antiangiogenic activity was evaluated by ELISA and immunohistochemistry analyses, which revealed that ES-NPs had a stronger antiangiogenic effect for reinforced anticancer activity. Indeed, even the treatment cycle in which ES-NPs were injected every seven days, showed stronger antitumor effect than the free ES injected for 14 consecutive days. Our study confirmed that the CS nanoparticle is a feasible carrier for endostatin to be used in the treatment of lung cancer.