ABSTRACT
Pancreatic cancer has the highest mortality among malignant cancers. Known asthe king of cancer,it lacks early symp-toms, diagnostic methods and oncologic markers. Early lymph node metastasis could be found in this disease. Moreover, advanced panereatic cancer is incurable by surgery. Due to the limited efficacy of surgery, as well as radiotherapy and chemotherapy tolerance, therapeutic methods for pancreatic cancer are being explored. L1 cell adhesion molecule (L1CAM) is a member of the cell adhesion molecule inmunoglobulin (Ig) super family that is usually expressed in normal developing nervous tissues. L1CAM is highly expressed in pancreatic cancer cells, binds withα5-integrin to activate downstream factors that mediate tumor metastasis and invasion via the TGF-β1/JUK/slug signaling pathway, induces epithelium-mesenchymal transition, and resists chemotherapy drugs. However, L1CAM forms abnormal vessels that increase the invasiveness of pancreatic cancer cells. This abnormal L1CAM expression in pancreatic can-cer cells is a new therapeutic target in pancreatic cancer treatment. Therefore, future studies on L1CAM could promote the develop-ment of pancreatic cancer therapy and provide new treatment methods.
ABSTRACT
Objective To explore the change of apoptosis factor Caspase-3 and Bcl-2 in the injured segment of rat with spinal cord injury after inhibiting lentivirus expression of inflammation factor TNF-α. To study the relationship between Caspase-3, Bcl-2, Bax and TNF-α in spinal cord injury. Mthods Spinal cord contusion model was prepared by Allen method. The relation between tumor necrosis factor alpha and Bcl-2, was predicted by the method of GeneMANIA bioinformatics. The RNA which was packaged by lentivirus constructed the RNA interference model of tumour necrosis factor alpha. After interference of tumor necrosis factor alpha, we used the method of QRT-PCR to assays the mRNA expression of Caspase-3 and Bcl-2 in spinal cord and detect of the localization of Caspase-3 and Bcl-2 by immunohistochemistry. Statistical analysis with SPSS17.0. Results SD rats had paraplegia and urinate retentaion because of spinal cord injury. The result of QRT-PCR showed that in the seventh day after SCC, the expression of Caspase-3 reduced significantly (P 0.05). Immunohistochemistry experiment results showed that Caspase-3 Bcl-2 and Bax immunoreactive cells were observed in the neurons and glial cells of both white matter and gray matter in the spinal cord. The results were the same with QRT-PCR.. Conclusion TNF-α in rats after SCC can effectively regulate the ratio of Bcl-2 and Bax , and then regulate the expression of Caspase-3 , which may affect the function of apoptosis and function recovery after spinal cord injury.
ABSTRACT
NESCA, a newly discovered signaling adapter protein in the NGF-pathway, contains a RUN domain at its N-terminus. Here we report the crystal structure of the NESCA RUN domain determined at 2.0-Å resolution. The overall fold of the NESCA RUN domain comprises nine helices, resembling the RUN domain of RPIPx and the RUN1 domain of Rab6IP1. However, compared to the other RUN domains, the RUN domain of NESCA has significantly different surface electrostatic distributions at the putative GTPase-interacting interface. We demonstrate that the RUN domain of NESCA can bind H-Ras, a downstream signaling molecule of TrkA, with high affinity. Moreover, NESCA RUN can directly interact with TrkA. These results provide new insights into how NESCA participates in the NGF-TrkA signaling pathway.