The anti-cancer properties of heparin and its derivatives: a review and prospect.

Heparin, including unfractionated heparin (UFH), low-molecular-weight heparin (LMWH) and heparin derivatives, are commonly used in venous thromboembolism treatment and reportedly have beneficial effects on cancer survival. Heparin can affect the proliferation, adhesion, angiogenesis, migration and invasion of cancer cells via multiple mechanisms. The main mechanisms involve inhibition of heparanase, P-/L-selectin, angiogenesis, and interference with the CXCL12-CXCR4 axis. Here we summarize the current experimental evidence regarding the anti-cancer role of heparin and its derivatives, and conclude that there is evidence to support heparin's role in inhibiting cancer progression, making it a promising anti-cancer agent.

Methionine Functionalized Biocompatible Block Copolymers for Targeted Plasmid DNA Delivery.

Reversible addition-fragmentation chain transfer (RAFT) polymerization integrates the advantages of radical polymerization and living polymerization. This work presents the preparation of methionine functionalized biocompatible block copolymers via RAFT polymerization. Firstly, N,N-bis(2-hydroxyethyl)methacrylamide-b-N-(3-aminopropyl)methacrylamide (BNHEMA-b-APMA, BA) was synthesized via RAFT polymerization using 4,4'-azobis(4-cyanovaleric acid) (ACVA) as an initiating agent and 4-cyanopentanoic acid dithiobenzoate (CTP) as the chain transfer agent. Subsequently, N,N-bis(2-hydroxyethyl)methacrylamide-b-N-(3-guanidinopropyl)methacrylamide (methionine grafted BNHEMA-b-GPMA, mBG) was prepared by modifying amine groups in APMA with methionine and guanidine groups. Three kinds of block polymers, mBG1, mBG2, and mBG3, were synthesized for comparison. A ninhydrin reaction was used to quantify the APMA content; mBG1, mBG2, and mBG3 had 21%, 37%, and 52% of APMA, respectively. Gel permeation chromatography (GPC) results showed that BA copolymers possess molecular weights of 16,200 (BA1), 20,900(BA2), and 27,200(BA3) g/mol. The plasmid DNA (pDNA) complexing ability of the obtained block copolymer gene carriers was also investigated. The charge ratios (N/P) were 8, 16, and 4 when pDNA was complexed completely with mBG1, mBG2, mBG3, respectively. When the N/P ratio of mBG/pDNA polyplexes was higher than 1, the Zeta potential of mBG was positive. At an N/P ratio between 16 and 32, the average particle size of mBG/pDNA polyplexes was between 100-200 nm. Overall, this work illustrates a simple and convenient protocol for the block copolymer carrier synthesis.

[Percutaneous vertebroplasty and open vertebroplasty for metastatic spinal tumor].

OBJECTIVE: To explore the clinical application and therapeutic effect of percutaneous vertebroplasty(PVP) and open vertebroplasty for metastatic spinal tumor. METHODS: The clinical data of 126 patients with metastatic spinal tumor underwent surgery and obtained follow-up from January 2012 to March 2016 were retrospectively analyzed. These 126 cases were divided into two groups according to different operative methods. The metastatic tumor of 43 cases encroached vertebral canal oppressing spinal cord and nerve root, they were treated with open operation(open vertebroplasty group);and other 83 cases without obviously spinal cord or nerve root compression, or unfit for open operation, were treated with PVP (percutaneous vertebroplasty group) . VAS score, ECOG and Frankel grade were used to evaluate the pain and neurofunction in two groups.All out-hospital patients were followed up every 3 months for 1 time. X-ray, CT, MRI were examined in follow-up. RESULTS: A total of 112 vertebrae underwent PVP with the median surgical time of 50 min;VAS scores decreased significantly at 2 days after operation, which maintained till 1 month later; ECOG grade at 1 month decreased significantly;44 of 112 vertebrae suffered from asymptomatic bone cement leakage, no complications such as nerve injury or pulmonary embolism was found; the median survival time was 16 months. While for open vertebroplasty group, the median surgical time was 160 min and blood loss was 1 000 ml; postoperative VAS scores and ECOG grade at 1 month decreased significantly. Postoperative Frankel grade of 36 patients got improvement in 41 patients with spinal cord functional disturbance(87.8%); and 29 of 40 patients with incompleteness out of motor function were full recovery(76.3%); 12 cases (27.9%) occurred complications and the median survival time was 11 months. CONCLUSIONS: The different vertebroplasty treatments can be selected for patients with metastatic spinal tumor, which can relieve the pain, improve the nerve function, reconstruct the spinal stabilization, maintain the local control and raise the life quality.

[Analysis of surgical treatment and effect of spinal metastatic tumors].

OBJECTIVE: To investigate clinical outcome of surgical treatment for spinal metastatic tumors. METHODS: Thirty-six patients with metastatic spine tumors treated surgically were retrospectivly reviewed from September 2005 to August 2010. There were 15 males and 21 females with an average age of 58 years old (ranged, 27 to 79 years). The site of origin of primary cancer included the breast, prostate, colon, lung, liver, esophagus, kidney, carcinoma, bladder, and 10 patients were with unidentified primary cancer. Five lesions were located in the cervical spine, 17 in the thoracic spine, 13 in the lumbar spine and 1 in the sacral vertebrae. Preoperative evaluation was conducted according to Tokuhashi system: total score 0 to 8 in 9 cases, 9 to 11 in 25 cases, 12 to 15 in 2 cases. The surgical procedures, including PVP, tumor resection and decompression, titanium nets implant, artificial vertebra replacement, bone cement stuffiness and inter fixation, were performed based on Tokuhashi score, location of lesions and neurological symptoms. RESULTS: All the patients were followed up, and the during ranged from 2 months to 60 months with a mean time of 10.8 months. Pain relief was obtained in all patients after operation, and the VAS pain scores declined after operation. Among 14 patients suffering from spinal cord and nerve compromise, 12 patients improved 1 to 2 grades after surgery according to the Frankel grading system. According to the system of the ECOG performance status: 28 patients improved 1 to 2 grades in performance status after surgery. The postoperative survival rates at 3 months, 6 months, 1 year and 2 years were 97.2%, 63.9%, 38.9% and 16.7% respectively. Six patines had bone cement leakage after PVP, and none resulted in severe complications. CONCLUSION: According to single or multiple spinal metastases, neurological symptoms, spinal stability and patients' condition, the different surgical treatments can be selected for spinal metastatic patients, which can relieve pain, maintain or improve the neurological status, improve quality of life, improve survival rate of patients.