OBJECTIVETo detect the role of Vascular endothelial growth factor C (VEGF-C) in the interaction of tongue squamous cell carcinoma (TSCC) with the peri-carcinoma lymphatics.

METHODSTSCC cells were implanted on the chorioallantoic membrane (CAM), in which, group A was transfected by plasmid pREP7 including VEGF-C, group B was transfected by plasmid pREP7, and group C was Tca8113. Lymphatic vessels were stained by 5'-Nase. Morphologic analysis was used to evaluate the alteration of lymphatic vessels density (LVD), area and perimeter.

RESULTSThe transplanted tumor well on CAM. The expression of VEGF-C in group A was higher than that in control group B and C. The LVD, perimeter and area in group A were (5.3 +/- 0.41)/high-power field, (148 +/- 21) microm and (76.8 +/- 13.5) microm(2) respectively in group A, which were significantly higher than that of group B and C (P < 0.01), while there were no significant difference between group B and C.

CONCLUSIONSCAM is ideal model for the research of lymphatic vessels; Over-expression of VEGF-C could induce the dilatation and LVD increase of peri-tumor lymphatic vessels, which maybe one of the mechanisms that VEGF-C metastasis of TSCC through lymphatic vessels.

Animals ; Carcinoma, Squamous Cell ; pathology ; Cell Line, Tumor ; Chick Embryo ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Lymphatic Vessels ; drug effects ; pathology ; Neck ; Neoplasm Transplantation ; Tongue Neoplasms ; pathology ; Transfection ; Vascular Endothelial Growth Factor C ; genetics

OBJECTIVETo observe the therapeutic effect of CDglyTK gene mediated by radiation-inducible promoters in the treatment of buccal carcinoma in Golden Hamster.

METHODSAnimal models of buccal carcinoma in golden hamster were established by painting 0.5% dimethyl-benzanthracene. The plasmids pcDNA (+) 3.1/E-CDglyTK were transfected into tumors by lipofectamine. 24 h later, the tumors were exposed to 3 Gy irradiation. Animals were monitored at regular intervals for volume of tumors. CDglyTK mRNA was assayed by RT-PCR. Apoptosis and proliferating cell nuclear antigen were detected respectively by in situ end-labeling and immunohistochemical methods.

RESULTSCompared with control groups, the tumor was suppressed obviously by CDglyTK gene therapy combined with 3 Gy induction radiation. The expression of CDglyTK gene could be detected by RT-PCR in the transfected tumor, and up-regulation of CDglyTK expression was found in tumor exposed to radiation (P < 0.05). There was significant difference in apoptosis index or proliferation index between tumor without irradiation and tumor with irradiation (P < 0.05).

CONCLUSIONSThe radiation-inducible promoter can be served as a molecular switch to regulate the expression of CDglyTK gene in buccal carcinoma in golden hamster, and low dose induction radiation can significantly improve the therapeutic effects.

Animals ; Carcinoma, Squamous Cell ; diagnostic imaging ; therapy ; Cheek ; diagnostic imaging ; Cricetinae ; Cytosine Deaminase ; genetics ; Genes, Transgenic, Suicide ; genetics ; Genetic Therapy ; methods ; Mesocricetus ; Mouth Neoplasms ; radiotherapy ; therapy ; Promoter Regions, Genetic ; radiation effects ; Radiography ; Simplexvirus ; enzymology ; Thymidine Kinase ; genetics

In this study, untargeted metabolomics was conducted using the liquid chromatography-tandem mass spectrometry(LC-MS/MS) technique to analyze the potential biomarkers in the plasma of mice with heart failure with preserved ejection fraction(HFpEF) induced by a high-fat diet(HFD) and nitric oxide synthase inhibitor(Nω-nitro-L-arginine methyl ester hydrochloride, L-NAME) and explore the pharmacological effects and mechanism of Jiming Powder in improving HFpEF. Male C57BL/6N mice aged eight weeks were randomly assigned to a control group, a model group, an empagliflozin(10 mg·kg~(-1)·d~(-1)) group, and high-and low-dose Jiming Powder(14.3 and 7.15 g·kg~(-1)·d~(-1)) groups. Mice in the control group were fed on a low-fat diet, and mice in the model group and groups with drug intervention were fed on a high-fat diet. All mice had free access to water, with water in the model group and Jiming Powder groups being supplemented with L-NAME(0.5 g·L~(-1)). Drugs were administered on the first day of modeling, and 15 weeks later, blood pressure and cardiac function of the mice in each group were measured. Heart tissues were collected for hematoxylin-eosin(HE) staining to observe pathological changes and Masson's staining to observe myocardial collagen deposition. Untargeted metabolomics analysis was performed on the plasma collected from mice in each group, and metabolic pathway analysis was conducted using MetaboAnalyst 5.0. The results showed that the blood pressure was significantly lower and the myocardial concentric hypertrophy and left ventricular diastolic dysfunction were significantly improved in both the high-dose and low-dose Jiming Powder groups as compared with those in the model group. HE and Masson staining showed that both high-dose and low-dose Jiming Powder significantly alleviated myocardial fibrosis. In the metabolomics experiment, 23 potential biomarkers were identified and eight strongly correlated metabolic pathways were enriched, including linoleic acid metabolism, histidine metabolism, alpha-linolenic acid metabolism, glycerophospholipid metabolism, purine metabolism, porphyrin and chlorophyll metabolism, arachidonic acid metabolism, and pyrimidine metabolism. The study confirmed the pharmacological effects of Jiming Powder in lowering blood pressure and ameliorating HFpEF and revealed the mechanism of Jiming Powder using the metabolomics technique, providing experimental evidence for the clinical application of Jiming Powder in treating HFpEF and a new perspective for advancing and developing TCM therapy for HFpEF.
Male ; Mice ; Animals ; Heart Failure/metabolism* ; Powders ; Stroke Volume/physiology* ; Chromatography, Liquid ; NG-Nitroarginine Methyl Ester/therapeutic use* ; Mice, Inbred C57BL ; Tandem Mass Spectrometry ; Metabolomics ; Biomarkers ; Water