Bone metastases from hepatocellular carcinoma: clinical features and prognostic factors.

BACKGROUND: Bone metastases (BMs) from hepatocellular carcinoma (HCC) is an increasingly common disease in Asia. We assessed the clinical features, prognostic factors, and differences in outcomes related to BMs among patients with different treatments for HCC. METHODS: Forty-three consecutive patients who were diagnosed with BMs from HCC between January 2010 and December 2014 were retrospectively enrolled. The clinical features were identified, the impacts of prognostic factors on survival were statistically analyzed, and clinical data were compared. RESULTS: The median patient age was 54 years; 38 patients were male and 5 female. The most common site for BMs was the trunk (69.3%). BMs with extension to the soft tissue were found in 14 patients (32.5%). Most (90.7%) of the lesions were mixed osteolytic and osteoblastic, and most (69.8%) patients presented with multiple BMs. The median survival after BMs diagnosis was 11 months. In multivariate analyses, survival after BM diagnosis was correlated with Karnofsky performance status (P=0.008) and the Child-Pugh classification (P<0.001); BM-free survival was correlated with progression beyond the University of California San Francisco criteria (P<0.001) and treatment of primary tumors (P<0.001). BMs with extension to soft tissue were less common in liver transplantation patients. During metastasis, the control of intrahepatic tumors was improved in liver transplantation and hepatectomy patients, compared to conservatively treated patients. CONCLUSIONS: The independent prognostic factors of survival after diagnosis of BMs were the Karnofsky performance status and Child-Pugh classification. HCC patients developed BMs may also benefit from liver transplantation or hepatectomy.

Neuroprotective effects of rapamycin on spinal cord injury in rats by increasing autophagy and Akt signaling.

Rapamycin treatment has been shown to increase autophagy activity and activate Akt phosphorylation, suppressing apoptosis in several models of ischemia reperfusion injury. However, little has been studied on the neuroprotective effects on spinal cord injury by activating Akt phosphorylation. We hypothesized that both effects of rapamycin, the increased autophagy activity and Akt signaling, would contribute to its neuroprotective properties. In this study, a compressive spinal cord injury model of rat was created by an aneurysm clip with a 30 g closing force. Rat models were intraperitoneally injected with rapamycin 1 mg/kg, followed by autophagy inhibitor 3-methyladenine 2.5 mg/kg and Akt inhibitor IV 1 µg/kg. Western blot assay, immunofluorescence staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay were used to observe the expression of neuronal autophagy molecule Beclin 1, apoptosis-related molecules Bcl-2, Bax, cytochrome c, caspase-3 and Akt signaling. Our results demonstrated that rapamycin inhibited the expression of mTOR in injured spinal cord tissue and up-regulated the expression of Beclin 1 and phosphorylated-Akt. Rapamycin prevented the decrease of bcl-2 expression in injured spinal cord tissue, reduced Bax, cytochrome c and caspase-3 expression levels and reduced the number of apoptotic neurons in injured spinal cord tissue 24 hours after spinal cord injury. 3-Methyladenine and Akt inhibitor IV intervention suppressed the expression of Beclin-1 and phosphorylated-Akt in injured spinal cord tissue and reduced the protective effect of rapamycin on apoptotic neurons. The above results indicate that the neuroprotective effect of rapamycin on spinal cord injury rats can be achieved by activating autophagy and the Akt signaling pathway.

Osteosarcoma cell-intrinsic colony stimulating factor-1 receptor functions to promote tumor cell metastasis through JAG1 signaling.

Therapeutic antibodies or inhibitors targeting CSF-1R block colony stimulating factor-1/colony stimulating factor-1 receptor (CSF-1/CSF-R) signaling, and have shown remarkable efficacy in the treatment of cancer. However, little is known about tumor cell-intrinsic CSF-1R effects. Here, we show that human osteosarcomas contain CSF-1R-expressing cancer subpopulations, and demonstrate that osteosarcoma cell-intrinsic CSF-1R promotes growth in vitro and in vivo. CSF-1R inhibition in osteosarcoma cells by RNA interference suppresses cell proliferation and tumor growth in mice. Conversely, CSF-1R overexpression enhances cell proliferation and accelerates tumor growth. CSF-1R overexpression can significantly enhance osteosarcoma cell migration, invasion, and epithelial-mesenchymal transition (EMT), whereas silencing CSF-1R inhibits these processes. Microarray analysis suggests that jagged 1 (JAG1) can function as a downstream mediator of CSF-1R. Moreover, we report a signaling pathway involving CSF-1R and JAG1 that sustains osteosarcoma cell migration and invasion. Our results identify osteosarcoma cell intrinsic functions of the CSF-1R/JAG1 axis in dissemination of osteosarcoma cells.

Combination of methylprednisolone and rosiglitazone promotes recovery of neurological function after spinal cord injury.

Methylprednisolone exhibits anti-inflammatory antioxidant properties, and rosiglitazone acts as an anti-inflammatory and antioxidant by activating peroxisome proliferator-activated receptor-γ in the spinal cord. Methylprednisolone and rosiglitazone have been clinically used during the early stages of secondary spinal cord injury. Because of the complexity and diversity of the inflammatory process after spinal cord injury, a single drug cannot completely inhibit inflammation. Therefore, we assumed that a combination of methylprednisolone and rosiglitazone might promote recovery of neurological function after secondary spinal cord injury. In this study, rats were intraperitoneally injected with methylprednisolone (30 mg/kg) and rosiglitazone (2 mg/kg) at 1 hour after injury, and methylprednisolone (15 mg/kg) at 24 and 48 hours after injury. Rosiglitazone was then administered once every 12 hours for 7 consecutive days. Our results demonstrated that a combined treatment with methylprednisolone and rosiglitazone had a more pronounced effect on attenuation of inflammation and cell apoptosis, as well as increased functional recovery, compared with either single treatment alone, indicating that a combination better promoted recovery of neurological function after injury.

Results after surgical treatment of transtectal transverse acetabular fractures.

OBJECTIVE: To retrospectively evaluate the results of operative treatment of transtectal transverse fractures of the acetabulum. METHODS: From May 1990 to July 2006, 40 patients with displaced transtectal transverse fracture of the acetabulum were treated surgically. A mean postoperative follow-up of 88.6 months' (range, 16-121 months) was achieved in 37 patients. Final clinical results were evaluated by a modified Merle d'Aubigné and Postel grading system. Postoperative radiographic results were evaluated by the Matta criteria. Fracture and radiographic variables were analyzed to identify possible associations with clinical outcome. RESULTS: Fracture reduction was graded as anatomic in 31 patients, imperfect in 4 and unsatisfactory in 2. Two hips were diagnosed to have subtle instability by postoperative radiography. The clinical outcome was graded as excellent in 16 patients, good in 14, fair in 4 and poor in 3. The radiographic result was graded as excellent in 14 patients, good in 15, fair in 4 and poor in 4. There was a strong association between the final clinical and radiographic outcomes. Variables identified as risk factors for unsatisfactory results included residual displacement greater than 2 mm, comminuted fracture of the weight bearing dome, postoperative subtle hip instability and damage to the cartilage of the femoral head. CONCLUSION: The uncomplicated radiographic appearance of transtectal transverse fracture belies its complexity. Comminuted fracture of the weight bearing dome, unsatisfactory fracture reduction, subtle hip instability and damage to the cartilage of the femoral head are risk factors for the clinical outcome of transtectal transverse fracture of the acetabulum.

Comparison of the mini-midvastus with the mini-medial parapatellar approach in primary TKA.

A prospective randomized study was performed to compare the clinical and radiological results of primary total knee arthroplasties (TKAs) using a mini-midvastus approach or a mini-medial parapatellar approach in 134 patients. The mini-midvastus approach was used on 68 patients (group A) and the mini-medial parapatellar approach on 66 patients (group B). All knees were implanted with the same posterior-stabilized prosthesis by the same surgeon (T.-S.T.) with the same set of downsized instruments. Mean follow-up in both groups was 30.5 months (range, 24-48 months). Patients in group A achieved an active straight-leg raise and 90° of flexion significantly earlier (P=.017 and P=.025, respectively). However, no significant difference was detected between the groups with respect to range of movement and Knee Society scores at all the postoperative visits and at final follow-up (all, P>.05). In contrast, the tourniquet time was significantly longer in group A (P=.015), with a higher incidence of medialized tibial component (P=.031). We believe that the early clinical results are similar between the mini-midvastus and mini-medial parapatellar approach. The mini-medial parapatellar approach is easier to initially apply and provides better visualization for TKA.