Peroxiredoxin-1 promotes cell proliferation and metastasis through enhancing Akt/mTOR in human osteosarcoma cells.

Osteosarcoma is characterized by high propensity for metastasis, especially to the lung, which is the main cause of death. Peroxiredoxin-1 (PRDX1) plays significant roles in multiple processes of initiation and progression of tumorogenesis. However, whether PRDX1 participates in metastasis of osteosarcoma remains unknown. Here, we demonstrate that PRDX1 overexpressed in osteosarcoma tissues comparing to adjacent non-tumor tissues. Two independent cohorts of patients showed high level of PRDX1 correlated with clinicopathological features such as larger tumor size and advanced tumor metastasis stage. While patients with high PRDX1 level have poor prognosis. Notably, expression level of PRDX1 especially increased in lung lesion of osteosarcoma patients, indicating that PRDX1 may promote lung metastasis. Ectopic expression of PRDX1 promotes osteosarcoma cell migration and metastasis in vitro and in vivo, whereas knockdown of PRDX1 expression suppresses cell metastatic behaviors such as invasion and migration. Furthermore, we found that PRDX1 promotes cells metastasis through enhancing Akt/mTOR signal pathway. Taken together, our findings prove the important role of PRDX1 in the molecular etiology of osteosarcoma and suggest that PRDX1 may be a novel prognostic biomarker and therapeutic target for osteosarcoma.

Inhibiting ROS-TFEB-Dependent Autophagy Enhances Salidroside-Induced Apoptosis in Human Chondrosarcoma Cells.

BACKGROUND/AIMS: Autophagy modulation has been considered a potential therapeutic strategy for human chondrosarcoma, and a previous study indicated that salidroside exhibits significant anti-carcinogenic activity. However, the ability of salidroside to induce autophagy and its role in human chondrosarcoma cell death remains unclear. METHODS: We exposed SW1353 cells to different concentrations of salidroside (0.5, 1 and 2 mM) for 24 h. RT-PCR, Western-blotting, Immunocytofluorescence, and Luciferase Reporter Assays were used to evaluate whether salidroside activated the TFEB-dependent autophagy. RESULTS: We show that salidroside induced significant apoptosis in the human chondrosarcoma cell line SW1353. In addition, we demonstrate that salidroside-induced an autophagic response in SW1353 cells, as evidenced by the upregulation of LC3-II and downregulation of P62. Moreover, pharmacological or genetic blocking of autophagy enhanced salidroside -induced apoptosis, indicating the cytoprotective role of autophagy in salidroside-treated SW1353 cells. Salidroside also induced TFEB (Ser142) dephosphorylation, subsequently to activated TFEB nuclear translocation and increase of TFEB reporter activity, which contributed to lysosomal biogenesis and the expression of autophagy-related genes. Importantly, we found that salidroside triggered the generation of ROS in SW1353 cells. Furthermore, NAC, a ROS scavenger, abrogated the effects of salidroside on TFEB-dependent autophagy. CONCLUSIONS: These data demonstrate that salidroside increased TFEB-dependent autophagy by activating ROS signaling pathways in human chondrosarcoma cells. These data also suggest that blocking ROS-TFEB-dependent autophagy to enhance the activity of salidroside warrants further attention in treatment of human chondrosarcoma cells.

Survey of cervical cancer survivors regarding quality of life and sexual function.

OBJECTIVE: To investigate the quality of life (QOL) of cervical cancer survivors in China. METHODS: Cervical cancer survivors were selected from 4 Tertiary Provincial Hospitals in Changsha, Hunan Province. Enrolled were 140 patients who received cancer treatments in these hospitals from 2007 to 2010. The Functional Assessment of Cancer Therapy-Cervix (FACT-Cx) Questionnaire was used to assess the QOL of the participants. Spiritual well-being was evaluated with the Functional Assessment of Chronic Illness Therapy-Spiritual Well-being (FACIT-Sp). Sexual function was measured with the Female Sexual Functioning Index. RESULTS: The average total FACT-Cx score was 124.45 (70-157). The average FACT-general score was 112.39 (49-150), and the average FACIT-Sp score was 13.9 (2-33.6). The prevalence of sexual dysfunction in our participants was 78%. Factors that were associated with QOL in cervical cancer survivors included gastrointestinal symptoms, health insurance, age, sleep disorders, and the number of complications. Sexual function was affected by radiotherapy, age, type of surgery, sleep disorders, and occupation. CONCLUSION: The QOL and sexual function of cervical cancer survivors were lower than the general population. Treatment-related complications and sexual dysfunction significantly affected patients' QOL. Having health insurance was associated with better QOL. Sexual function was adversely affected by radiotherapy and radical hysterectomy.

[Effect of leptin on inducible NO and MMP-13 in rabbit articular chondrocytes in vitro].

OBJECTIVE: To observe the in vitro effect of leptin, alone or in combination with tumor necrosis factor-alpha (TNF-alpha) on inducible nitric oxide(NO)and on inducible matrix metalloproteinase-13 (MMP-13) in rabbit articular chondrocytes. METHODS: The chondrocytes from the articular cartilage of 2-month-old rabbits were cultivated and identified, and the second filial generation chondrocytes were cocultured on plates with different concentrations of leptin alone or in combination with TNF-alpha for 48 h or 96 h after 12 h starvation. The concentration of NO and MMP-13 was measured in the chondrocytes culture supernatant fluid. The results were statistically analyzed. RESULTS: There was no significant difference in the concentrations of NO between the different concentrations of leptin alone groups and the blank control group (P>0.05). In combination with the same concentration of TNF-alpha (10 ng/mL), leptin could dose-dependently increase the concentration of NO in the chondrocytes culture supernatant fluid in vitro. There was significant value in average concentration of MMP-13 on the main effect of both time and dose (P<0.05). No MMP-13 was detected in the blank control group. CONCLUSION: Leptin can induce MMP-13 and have synergistic induction effect on NO with TNF-alpha in rabbit articular chondrocytes in vitro.