Xiuxin Han

Comparison of FDG PET/CT and gadolinium-enhanced mri for the detection of bone metastases in patients with cancer: A meta-analysis

Objective At present, the differences in the efficacy between PET/CT and MRI for the detection of bone metastases in patients with cancer have not been clearly delineated. We performed a meta-analysis to compare the performance of FDG PET/CT with that of gadolinium-enhanced MRI for the detection of bone metastases in patients with cancer. Methods Studies about PET/CT and MRI for the detection of bone metastases were systematically searched in the MEDLINE, EMBASE, and EBM Review databases. We calculated sensitivities, specificities, diagnostic odds ratios, positive likelihood ratios, negative likelihood ratios (NLR), and constructed summary receiver operating characteristic curves using bivariate regression models for PET/CT and MRI, respectively. Results Across 9 studies (1116 patients), FDG PET/CT has similar patient-based sensitivity (0.803 vs 0.837), specificity (0.989 vs 0.977), diagnostic odds ratio (309.0 vs 221.9), positive likelihood ratio (61.7 vs 37.0), and negative likelihood ratio (0.200 vs 0.167) with gadolinium-enhanced MRI. Areas under the curve with 95% confidence interval for FDG PET/CT and gadolinium-enhanced MRI were 0.99 (0.98–0.99) and 0.98 (0.97–0.99), respectively. Conclusions FDG PET/CT and gadolinium-enhanced MRI have excellent diagnostic performance for the detection of bone metastases in patients with cancer.

PLA2G16 Expression in Human Osteosarcoma Is Associated with Pulmonary Metastasis and Poor Prognosis.

Background Osteosarcoma is the most frequent type of malignant bone tumor in children and adolescents and is associated with a high propensity for lung metastasis. Recent experiments have indicated that PLA2G16 contributes to osteosarcoma progression and metastasis in both mouse and human osteosarcoma cell lines. The aim of this study was to compare the expression of PLA2G16 in non-metastatic and metastatic osteosarcomas to determine whether PLA2G16 expression can serve as a biomarker of osteosarcoma prognosis and metastasis. Methods Quantitative real-time PCR was used to examine PLA2G16 mRNA in primary osteosarcoma patients (18 patients without metastases and 17 patients with metastases), and immunohistochemistry (IHC) staining of PLA2G16 was performed on tissue microarrays from 119 osteosarcoma patients. Tumor metastatic behavior and survival of the patients were followed up for a minimum of 36 months and a maximum of 171 months. The prognostic value of PLA2G16 expression was evaluated by the Kaplan–Meier method and a log-rank test. Multivariate Cox regression analysis was used to identify significant independent prognostic factors. Results Osteosarcoma patients with metastasis showed a higher expression of PLA2G16 at both the mRNA and protein levels (both at P values< 0.05) than did patients without metastasis. Osteosarcoma patients with positive IHC staining of PLA2G16 expression at primary sites had shorter overall survival and metastasis-free survival (both at P values <0.02). Moreover, multivariate Cox analysis identified PLA2G16 expression as an independent prognostic factor to predict poor overall survival and metastasis-free survival (both P values < 0.03). Conclusions This study indicated that PLA2G16 expression is a significant prognostic factor in primary osteosarcoma patients for predicting the development of metastases and poor survival.

PLA2G16 promotes osteosarcoma metastasis and drug resistance via the MAPK pathway

The prognosis of metastatic osteosarcoma is dismal and a better understanding of the mechanisms underlying disease progression is essential to improve treatment options and patient outcomes. We previously demonstrated Pla2g16 overexpression in mouse osteosarcoma contributes to metastasis phenotypes and increased expression of PLA2G16 is associated with metastasis and poor prognosis in human tumors. To further examine the mechanisms through which PLA2G16 contributes to human osteosarcoma metastasis and explore the potential of PLA2G16 as a therapeutic target in osteosarcoma, we generated a panel of human osteosarcoma cell lines expressing different levels of PLA2G16. The functional analyses of these cell lines demonstrated high levels of PLA2G16 expression increased osteosarcoma cell migration, invasion, clonogenic survival, and anchorage-independent colony formation. Importantly, this activity was dependent on the phospholipase activity of PLA2G16. Additionally, PLA2G16 overexpression decreased the sensitivity of cells to a panel of chemotherapeutic agents. Analysis of downstream pathways revealed the pro-metastasis functions of PLA2G16 were mediated through the MAPK pathway, as knockdown of PLA2G16 decreased ERK1/2 phosphorylation and pharmacological inhibition of MEK significantly repressed PLA2G16 mediated cell migration and clonogenic survival. Furthermore, PLA2G16 overexpression promoted xenograft tumor growth in vivo, and these tumors exhibit increased ERK1/2 phosphorylation. Lastly, the expression of PLA2G16 is strongly correlated with the increased ERK1/2 phosphorylation in human osteosarcoma samples, and the combined lesions are associated with reduced overall and metastasis-free survival. Collectively, these results demonstrate increased PLA2G16 expression activates the MAPK pathway to enhance osteosarcoma metastasis and may be a novel therapeutic target for these cancers.

Recombined humanized endostatin (Endostar) combined with chemotherapy for advanced bone and soft tissue sarcomas in stage IV

Purpose This retrospective case-series study evaluated efficacy and safety of Endostar combined with chemotherapy in the treatment of advanced bone and soft tissue sarcomas in stage IV. Materials and Methods Forty-seven patients diagnosed with stage IV bone and soft tissue sarcomas and treated with chemotherapy in Tianjin Medical University Cancer Institute & Hospital were reviewed. Of these patients, 23 patients were treated with Endostar plus chemotherapy (designated as combined group), and 24 patients received only chemotherapy (designated as control group). Progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and clinical benefit response (CBR) were analyzed to find the difference between these two groups with the purpose to investigate the role of Endostar in metastatic sarcomas. Results Endostar combined with chemotherapy had significantly increased PFS. In the combined group and control groups, the median PFS (8.6 months versus 4.4 months) and the CBR (47.8% versus 16.7%) showed significant difference (P = 0.032), while the median overall survival (11.7 months versus 10.6 months, P = 0.658) and the ORR (17.4% versus 8.3%, P = 0.167) showed no significant difference. The common grade 3-4 side effects for both groups were myelosuppression and transient elevation of transaminases. Conclusion Endostar combined with chemotherapy had significant activity to increase the PFS and improve CBR in patients with advanced sarcomas, with tolerable side effects.

Diffusion Tensor Imaging in Diagnosis of Post-Traumatic Syringomyelia in Spinal Cord Injury in Rats

Background Post-traumatic syringomyelia (PTS) is a common disease after spinal cord injury (SCI). The present study was performed to evaluate the advantages of diffusion tensor imaging (DTI) in estimating SCI and prognosing PTS in SCI rats. Material/Methods Forty rats were divided into 3 groups based on the extent of the individual SCI and PTS: a control group (n=10), a PTS group (n=8), and an SCI group (n=22). BBB tests were performed preoperatively and postoperatively at (1 d, 3 d, 5 d, 1 w, 2 w, 1 w, 2 w, 3 w, 4 w, 5 w, and 6 w). MRI T2 scanning was conducted postoperatively at (1 w, 2 w, 3 w, 4 w, 5 w, 6 w). DTI and diffusion tensor tractography were used for analyzing neuro-fiber changes after SCI. Results BBB scoring showed no differences between the PTS group and SCI group (P<0.05). PTS was found in 8 rats after SCI. MRI showed PTS formation in 3 rats at 2 w after SCI, and 5 rats showed PTS formation at postoperative 3w after SCI. Compared with the control group, ADC showed significant increase in both the PTS group (P<0.05) and the SCI group (P<0.05), FA showed significant decreases in the PTS (P<0.05) and SCI (P<0.05) groups. Compared with the SCI group, the PTS group showed an increase in ADC, but no statistical difference was found in ADC (P>0.05). The PTS group showed a significant increase in FA (P<0.05). Conclusions The combination of diffusion tensor imaging and diffusion tensor tractography has characteristics of high-sensitivity and quantitation for PTS prognosis. FA is predictive in the prognosis of PTS formation after SCI.

SIAH1/ZEB1/IL-6 axis is involved in doxorubicin (Dox) resistance of osteosarcoma cells

Abstract Osteosarcoma (OS) patients often exhibit pulmonary metastasis, which results in high patient mortality. Our present study established the doxorubicin (Dox) resistant human OS MG-63 and HOS cells and named them MG-63/Dox and HOS/Dox, respectively. The Dox resistant OS cells had greater invasion ability than that of parental cells. The expression of ZEB1, while not FOXM1, Snail, HIF-1α, or Sp1, was significantly increased in Dox resistant OS cells. Silencing of ZEB1 can attenuate the metastasis and increase Dox sensitivity of MG-63/Dox and HOS/Dox cells. The upregulation of ZEB1 can increase of the expression of interlukin-6 (IL-6). Anti-IL-6 inhibited the invasion and increase the Dox sensitivity of MG-63/Dox and HOS/Dox cells. There was no significant difference of ZEB1 mRNA between Dox resistant and control cells. The upregulation of ZEB1 in Dox resistant OS cells can be attributed to the increase of protein half-life. This was confirmed by results that the inhibitor of proteasomal degradation can increase ZEB1 in Dox resistant OS cells. Over expression of SIAH1 can inhibit the expression of ZEB1 and increase the Dox sensitivity of MG-63/Dox and HOS/Dox cells. Collectively, we confirmed that SIAH1 induced ZEB1 is involved in the Dox resistance of OS cells.

Comparison of the therapeutic effects of surgery combined with postoperative radiotherapy and standalone radiotherapy in treating spinal metastases of lung cancer

OBJECT There are few studies comparing the therapeutic efficacy between surgery combined with postoperative radiotherapy and standalone radiotherapy in treating spinal metastases of lung cancer. The aim of this clinical study was to compare the clinical and functional efficacy, quality of life, and survival outcomes between surgery combined with postoperative radiotherapy and standalone radiotherapy in treating spinal metastases of lung cancer. METHODS A retrospective analysis of clinical data from June 2008 to December 2013 was performed with 46 patients suffering spinal metastases of lung cancer. Among the studied patients, 25 patients received standalone radiotherapy (radiotherapy group), and the other 21 patients received surgery combined with postoperative radiotherapy (surgery group). Follow-up and survival time were analyzed. Pain levels of the patients were assessed by visual analogue scale (VAS) from pre-treatment to one month and three months after starting treatment. 3 months after surgery, Neurologic deficit of the patients was evaluated using Frankel Grade, and functional impairment were classified by Karnofsky Score. The quality of life (QOL) was assessed by EORTC QLQ-C30 questionnaire. RESULTS The follow-up period of the patients ranged from 2 to 25 months with the average of 8.8 months. In radiotherapy group, the mean survival was 8.5 months with median survival time of 7.8 months. In surgery group, the mean survival was 10.6 months with median survival of 8.4 months. The difference in survival times between the two groups was not statistically significant (P=0.24>0.05). From pre-treatment to one month and three months after treatment initiation, the VAS in both groups showed statistical significant improvement (One month: P<0.01 Three months: P=0.001, p<<0.01). In the surgery group, 85.7% of all patients had functionally useful Frankel Grade D or E after surgery, compared with 71.4% pre-operatively. The percentage was 72.0% in the radiotherapy group post-treatment, compared with 68.0% pre-treatment. The relief of Frankel Grade in surgical group was superior to that of the radiotherapy group (p=0.025, p<0.01). KPS score (80-100) percentages in surgery group and in radiotherapy group were increased by 19% and 13.3%, respectively. The improvement of KPS was more in the surgery group (p=0.013, P<0.01). In radiotherapy group, the EORTC QLQ-C30 score was 86.13 ± 12.11 before treatment and 68.39 ± 14.96 after treatment. In surgery group, the EORTC QLQ-C30 score was 84.09 ± 9.48 before treatment and 54.64 ± 15.17 after treatment. The improvement of patient QOL was more in the surgery group (p=0.004, p<0.01). CONCLUSION Compared with standalone radiotherapy, surgery combined with postoperative radiotherapy did not significantly prolong the survival time. However, surgery can improve pain, function and QOL of patients with spinal metastases of lung cancer.