Correlation between TEM1 expression and efficacy of neoadjuvant chemotherapy in patients with gastric cancer / 中国肿瘤临床

Objective: To detect the expression of P53, human epidermal growth factor receptor-2 (HER-2), and tumor endothelial marker 1 (TEM1) in gastric cancer tissues, analyze their correlation with clinical efficacy, and explore their potential roles as biomarkers for neoadjuvant chemotherapy. Methods: Sixty-three patients with gastric cancer who underwent fluorouracil-based neoadjuvant che-motherapy in The First Hospital of Lanzhou University from May 2015 to May 2017 were enrolled. Using immunohistochemistry, the expression of P53, Her2, and TEM1 was detected in 63 gastric cancer specimens before neoadjuvant chemotherapy. The efficacy of neoadjuvant chemotherapy was assessed by imaging. The relationship between the expression of P53, HER-2, and TEM1 and the effi-cacy of neoadjuvant chemotherapy was analyzed. Results: The total effective rate of neoadjuvant chemotherapy in 63 patients with advanced gastric cancer was 69.8%, with 2, 7, and 35 patients achieving complete remission, partial remission, and stable disease, re-spectively. Disease progression was noted in 19 patients. Univariate analysis revealed that patients positive for TEM1 and having high T stage had a poor response to neoadjuvant chemotherapy (P<0.05); furthermore, location, differentiation, and size of tumor; P53 posi-tivity (P=0.488); and Her-2 positivity (P=0.106) were not associated with the efficacy of neoadjuvant chemotherapy for gastric cancer. Multivariate analysis revealed that TEM1 positivity and a higher T stage could be factors that predicted the response to neoadjuvant chemotherapy in patients with advanced gastric cancer. Conclusions: TEM1, as a marker of tumor stroma, may be an important molec-ular biological indicator that predicts the poor response to neoadjuvant chemotherapy in patients with gastric cancer.

Over-expression of miR-488-5p decreases proliferation and migration ability of cervical cancer C33Acells through TEM8 / 中国肿瘤生物治疗杂志

@# Objective: To observe the expression of miR-488-5p in cervical cancer tissues and to explore its effect on the proliferation and migration of cervical cancer C33Acells. Methods: 12 pairs of cervical cancer tissues and corresponding paracancer tissues from patients, who underwent total hysterectomy at the Luoyang Central Hospital of Zhengzhou University from March 2017 to September 2017, were collected for this study; and the expression of miR-488-5p was detected by fluorescence quantitative and real-time polymerase chain reaction (qRT-PCR). Lipofectamine 3000 was used to transfect miR-488-5p (experiment group) and miR-NC (control group) into cervical cancer C33Acells. Cell cycle distribution was detected by Flow cytometry. Cell proliferation was assessed by CCK8 assay and Transwell assay was used to detect cell migration. Bioinformatics software was used to predict the possible target genes of miR-488-5p, and luciferase activity assay was used to verify the binding of miR-488-5p to target genes. The expressions of tumor endothelial marker 8 (TEM8) and downstream EGFR signaling pathway related proteins in two groups were detected by qRT-PCR and Western blotting. Results: The relative expression level of miR-488-5p in cervical cancer tissues (1.33±0.20) was significantly lower than that in paracancer tissues (3.68±0.45) (P<0.01). The relative expression level of miR-488-5p in the experimental group (25.23±3.11) was significantly higher than that in the control group (1.02±0.10) (P<0.01). The percentage of C33A cells at G0/G1 phase in experimental group (53.39±2.48)% was significantly higher than that in control group (39.57±1.21)% (P<0.01). When the culture time extended to 96 h and 120 h, the proliferation ability of C33Acells in experimental group was significantly lower than that in control group (P<0.05), and the number of migrated cells in the experimental group (117.90±18.86) was significantly less than that in the control group (295.10±19.33) (P <0.01). Luciferase activity assay confirmed that miR-488-5p could directly bind with TEM8 and inhibit its expression (P<0.01). The relative expression of TEM8 mRNAin experimental group (0.42±0.06) was significantly lower than that in control group (1.00 ± 0.06) (P<0.01).After transfection with miR-488-5p for 48h, the protein expressions of TEM8, p-EGFR, p-ERK and pAKT were significantly lower than those in control group (P <0.01). Conclusion: The expression of miR-488-5p in cervical cancer tissues was decreased. Over-expression of miR-488-5p could inhibit the cell cycle progression of cervical cancer cells and reduce the proliferation and migration of cervical cancer cells. The mechanism may be related to the interference of TEM8 gene expression.

Nidogen Plays a Role in the Regenerative Axon Growth of Adult Sensory Neurons Through Schwann Cells

We previously reported that nidogen is an extracellular matrix protein regulating Schwann cell proliferation and migration. Since Schwann cells play a critical role in peripheral nerve regeneration, nidogen may play a role in it via regulation of Schwann cells. Here, we demonstrate direct evidence that nidogen induces elongation of regenerative axon growth of adult sensory neurons, and that the effect is Schwann cell dependent. Continuous infusion of recombinant ectodomain of tumor endothelial marker 7, which specifically blocks nidogen function in Schwann cells, suppressed regenerative neurite growth in a sciatic nerve axotomy model. Taken together, it is likely that nidogen is required for proper regeneration of peripheral nerves after injury.

Expression Profile of Tumor Endothelial Marker 7 and a Putative Ligand in the Rat Spinal Cord and Dorsal Root Ganglion

STUDY DESIGN: To analyze the expression profile of tumor endothelial marker 7 (TEM7) in the spinal cord and dorsal root ganglion (DRG). PURPOSE: To investigate the expression profile of TEM7 in the spinal cord and DRG of adult and developing rats. OVERVIEW OF LITERATURE: Tumor endothelial marker 7 (TEM7) is a putative transmembrane protein that is highly expressed in the tumor endothelium and in cerebellar neurons. METHODS: In the present study, the expression profile of TEM7 in the spinal cord and DRG of the rat was investigated using in situ hybridization and immunohistochemical analysis. In addition, the secreted recombinant ectodomain of TEM7 was employed to label the expression of a putative ligand of TEM7 in the spinal cord and DRG. RESULTS: Specific TEM7 mRNA localization was observed in the motor neurons of the spinal cord and sensory neurons of the DRG. Glial cells and vascular endothelial cells did not show hybridization signals. Immunohistochemical analysis with a specific polyclonal antibody revealed a similar localization profile for TEM7 mRNA expression. In the spinal cord, weak labeling was observed in the gray matter. The TEM7 ectodomain localized the expression of a putative ligand of TEM7 in the neurilemmal structures and perineurium of the spinal nerve roots. In the DRG, ligand labeling was observed in the endoneurium and perineurium of the spinal nerves, and extracellular matrix around the sensory neurons. A developmental study has shown that TEM7 mRNA expression in the motor neurons of the spinal cord and DRG increased with age during postnatal development. Conclusion: These findings indicate that TEM7 plays a role as a transmembrane receptor in neuronal populations of the spinal cord and DRG.