However, the key points have not been well elucidated, and the investigation of mechanisms for multiple HCC may improve the prognosis of this severe disease. Brain-derived neurotrophic factor (BDNF) is a member of nerve growth factor family, playing an important role in supporting survival and growth of neurons. Epigenetics inhibitor Tropomysin-related kinase B (TrkB) is the primary receptor of BDNF, which functions as a tyrosine kinase. BDNF and TrkB are up-regulated in a variety of primary human tumors,
including neuroblastoma , breast , bladder  and ovarian  cancers. In gastric cancer, a high level of TrkB expression was predicted for distant metastases and poor prognosis . TrkB overexpression was also found in highly metastatic pancreatic cancer cells, which was presumed to mediate the clinical features of aggressive growth and metastasis of pancreatic Fosbretabulin cost cancer . When activated by BDNF, TrkB induces the activation of downstream signaling molecules, such as
Akt [11, 12] and ERK [13, 14], which elicits the differential regulation of various cellular activities, like cell proliferation , differentiation , apoptosis , and invasion . TrkB signaling promotes cell survival in an anchorage-independent manner . In HCC, the expressions of BDNF and TrkB were found up-regulated in detached HCC BEL7402 cell aggregations, which were able to resistant to detachment-induced apoptosis . Despite the increasing evidence of BDNF and TrkB on tumor progression, whether they are involved
in multiple HCC has not yet been determined. In the present study, the expressions of BDNF and TrkB in HCC specimens were examined, and by neutralizing BDNF or inhibiting Bacterial neuraminidase TrkB kinase activity in HCC cell lines to observe the effects of BDNF/TrkB interruption on cell apoptosis and invasion. Methods HCC samples A total of 65 HCC patients who had therapeutic resection from January 2006 to January 2011 were enrolled in this study. This study was approved by the Medical Research Ethics Committee of China Medical University and the informed consent was obtained from all patients. All of the enrolled patients underwent curative surgical resection without having chemotherapy or radiation therapy. Formalin-fixed paraffin-embedded sections of tumor were stained routinely with hematoxylin and eosin (HE), and reviewed by two senior pathologists in order to determine the histological characteristics and tumor stage according to the AJCC/UICC TNM staging system (2003, Edit 6). Clinicopathological information including tumor distribution (solitary or multiple nodules), differentiation, stage and lymph node metastasis was obtained from patient records, and listed in additional file 1. Immunohistochemistry 65 paraffin sections of HCC were deparaffinized and rehydrated routinely.