Telomeres and telomerase in Sarcoma disease and therapy.

Sarcoma is a rare tumor derived from the mesenchymal tissue and mainly found in children and adolescents. The outcome for patients with sarcoma is relatively poor compared with that for many other solid malignant tumors. Sarcomas have a highly heterogeneous pathogenesis, histopathology and biological behavior. Dysregulated signaling pathways and various gene mutations are frequently observed in sarcomas. The telomere maintenance mechanism (TMM) has recently been considered as a prognostic factor for patients with sarcomas, and alternative lengthening of telomeres (ALT) positivity has been correlated with poor outcomes in patients with several types of sarcomas. Therefore, telomeres and telomerases may be useful targets for treating sarcomas. This review aims to provide an overview of telomere and telomerase biology in sarcomas.

Prognostic analysis of percutaneous vertebroplasty (PVP) combined with 125I implantation on lumbosacral vertebral osteoblastic metastases.

OBJECTIVE: Lumbosacral vertebral osteoblastic metastasis is treated with percutaneous vertebroplasty (PVP) combined with 125I seed implantation and PVP alone. Compared to PVP alone, we evaluated the effects of combination therapy with PVP and 125I seed implantation on pain, physical condition, and survival and evaluated the clinical value of PVP combined with 125I particle implantation. METHODS: We retrospectively analyzed 62 patients with lumbosacral vertebral osseous metastases treated at our hospital between 2016 and 2019. All the patients met the inclusion criteria for 125I implantation, and they were randomly divided into a combined treatment group and a pure PVP surgery group. The visual analog pain scale (VAS), Karnofsky Performance Status (KPS), and survival time were recorded at different time points, including preoperative, postoperative 1 day, 1 month, 3 months, 6 months, 12 months, and 36 months in each group. The variation in clinical indicators and differences between the groups were analyzed using SPSS version 20.0. Correlations between different variables were analyzed using the nonparametric Spearman's rank test. The Kaplan-Meier method was used to estimate the relationship between survival time and KPS score, VAS score, or primary tumor progression, and survival differences were analyzed using the log-rank test. Multivariate analyses were performed using a stepwise Cox proportional hazards model to identify independent prognostic factors. RESULTS: Compared to the PVP treatment group, the pain level in the combined treatment group was significantly reduced (P = 0.000), and the patient's physical condition in the combination treatment group significantly improved. Kaplan-Meier analysis showed that the survival rate of the PVP group was significantly lower than that of the combination group (P = 0.038). We also found that the median survival of patients in both groups significantly increased with an increase in the KPS score (14 months vs. 33 months) (P = 0.020). Patients with more than three transfer sections had significantly lower survival rates than those with one or two segments of the section (P = 0.001). Further, Cox regression analysis showed that age (P = 0.002), the spinal segment for spinal metastasis (P = 0.000), and primary tumor growth rate (P = 0.005) were independent factors that affected the long-term survival of patients with lumbosacral vertebral osseous metastases. CONCLUSIONS: PVP combined 125I seeds implantation surgery demonstrated superior effectiveness compared to PVP surgery alone in treating lumbosacral vertebral osseous metastases, which had feasibility in the clinical operation. Preoperative KPS score, spine transfer section, and primary tumor growth rate were closely related to the survival of patients with lumbosacral vertebral osteoblastic metastasis. Age, spinal segment for spinal metastasis, and primary tumor growth can serve as prognostic indicators and guide clinical treatment.

Upregulated lncRNA ADAMTS9-AS2 suppresses progression of lung cancer through inhibition of miR-223-3p and promotion of TGFBR3.

In this study, we aimed at investigating effects of lncRNA ADAMTS9-AS2 on lung cancer progression through regulating miR-223-3p and TGFBR3 expressions. Expressions of ADAMTS9-AS2 in lung cancer tissues and cell lines were determined by reverse transcriptase polymerase chain reaction (qRT-PCR). TargetScan and miRcode were used to predict the targeting relationships, respectively. The luciferase reporter system was used to verify that the relationship among ADAMTS9-AS2, TGFBR3 and miR-223-3p. Western blot assay tested the protein level changes in TGFBR3. Cell proliferation was determined by CCK-8 assay. Cell cycle and cell apoptosis were detected by flow cytometry assay, and migration and invasion were determined by transwell assay. Tumor xenograft model was developed to study the influence of ADAMTS9-AS2 on tumor growth in vivo. qRT-PCR results demonstrated that lncADAMTS9-AS2 was lowly expressed in lung cancer tissues. High expression of ADAMTS9-AS2 in lung cancer cells significantly reduced proliferation ability and inhibited migration, as well as elevating their apoptosis rate. In vivo assay found that ADAMTS9-AS2 suppressed the lung tumor growth. Bioinformatics predicted that miR-223-3p bound directly to the ADAMTS9-AS2 and TGFBR3, which was later confirmed by luciferase reporter system. ADAMTS9-AS2 transfection increased TGFBR3 mRNA and protein expressions in lung cancer cells, but miR-223-3p transfection significantly decreased them. Besides, our results showed that miR-223-3p induced cellular apoptosis while TGFBR3 group showed the complete opposite effect. It was proved that ADAMTS9-AS2 and TGFBR3 were the direct genes of miR-223-3p. MiR-223-3p promotes proliferation, migration and invasion of lung cancer cells by targeting TGFBR3. Therefore, ADAMTS9-AS2, miR-223-3p and TGFBR3 may provide potential targets for the treatment of lung cancer patients. © 2018 IUBMB Life, 70(6):536-546, 2018.

Thoracolumbar paravertebral giant ganglioneuroma and scoliosis: a case report and literature review.

Paravertebral ganglioneuroma and scoliosis is a rare clinical benign disease. The case we reported is about a 12-year-old girl who was hospitalized due to neoplasm with spinal deformity in the right abdomen for 1 month. Based on a careful preoperative evaluation and found no obvious surgery contraindications, the patient was treated with surgical resection of the tumor and correction of the deformity by surgery. Postoperative pathologic examination confirmed it was a ganglioneuroma. After the operation, the patient recovered well. Her spinal deformity was corrected, and she was 5 cm taller. Complete resection of ganglioneuroma following with a low recurrence rate and a good prognosis, patient does not need further chemotherapy, radiation therapy, or other treatments. All follow-up radiographic studies demonstrated no relapse of the tumor in the following 18 months. Combining this case with similar cases at home and aboard and reviewing related literature, we formed conclusions based on the manifestations, diagnosis, treatment, and prognosis of this disease and provided treatments for similar cases.

Surgery methods and soft tissue extension are the potential risk factors of local recurrence in giant cell tumor of bone.

BACKGROUND: Various treatments of giant cell tumor of bone (GCTB) included in curettages and resections and with adjuvant are exerted, but the best treatment is controversial. The aim of the study was the identification of individual risk factors after various treatments in GCTB. METHODS: A total of 179 patients treated for GCTB between 1998 and 2010 were concluded in the retrospective study. All patients were treated with intralesional curettage, extensive curettage, or wide resection. Mean follow-up was 60.2 ± 18.7 months (36~112 months). Age, gender, tumor location, Campanacci grade, soft tissue extension, pathological features, and surgical methods were performed to univariate Kaplan-Meier survival analysis and multivariate Cox regression analysis. RESULTS: The local recurrence rates of intralesional curettage (41.9%) and extensive curettage (19.0%) were significantly higher than that of wide resection (7.7%). The higher risk of local recurrence was found for soft tissue extension (hazard = 7.921, 95% CI 1.107~56.671), compared with no statistical significances between gender, location, Campanacci grade, pathologic fracture, and local recurrences, which were shown by Kaplan-Meier analysis. However, recurrence-free survival (RFS) of patients younger than 30 was significantly lower than that of patients older than 30. The RFS of pathologic fracture patients with soft tissue extension was significantly lower than that of pathologic fracture patients without soft tissue extension. Multivariate Cox regression analysis indicated that the independent variable that contributed to recurrence-free survival was soft tissue extension and surgical methods. The RFS of extensive curettage had no statistically significant difference with wide resection and was significantly higher than that of intralesional curettage. Use of high-speed burring and bone cement significantly decreased the local recurrence rate. CONCLUSIONS: Age (below 30 years), gender, tumor location, Campanacci grade, and pathologic fracture have no statistically significant influence on local recurrences. Soft tissue extension and intralesional curettage of surgical methods increased the RFS. The results of the present study suggested that compared with curettage and wide section, treatment of GCTB by extensive curettage could provide the favorable local control and functional recovery.

Apoptosis, autophagy, necroptosis, and cancer metastasis.

Metastasis is a crucial hallmark of cancer progression, which involves numerous factors including the degradation of the extracellular matrix (ECM), the epithelial-to-mesenchymal transition (EMT), tumor angiogenesis, the development of an inflammatory tumor microenvironment, and defects in programmed cell death. Programmed cell death, such as apoptosis, autophagy, and necroptosis, plays crucial roles in metastatic processes. Malignant tumor cells must overcome these various forms of cell death to metastasize. This review summarizes the recent advances in the understanding of the mechanisms by which key regulators of apoptosis, autophagy, and necroptosis participate in cancer metastasis and discusses the crosstalk between apoptosis, autophagy, and necroptosis involved in the regulation of cancer metastasis.

Safety of percutaneous vertebroplasty for the treatment of metastatic spinal tumors in patients with posterior wall defects.

PURPOSE: To assess the clinical effect of percutaneous vertebroplasty (PVP) in the treatment of metastatic spinal tumors in patients with posterior wall defect. METHODS: The treated vertebrae bodies were divided into four groups: group A, non-posterior vertebral wall defect; group B, posterior vertebral wall with cribriform defects; group C, posterior vertebral wall with local fragmentation defects; group D, posterior vertebral wall with severe defects. The injected volume of bone cement, visual analogue scale (VAS) score, Karnofsky Performance Scale (KPS), cement leakage and survival were analyzed. RESULTS: The injected volume of bone cement for group A was significantly higher than posterior wall defect group (including group B, C, and D). No significant differences about the injected volume of bone cement among the posterior wall defect groups. The incidence of bone cement leakage for group A was not significantly different as compared to posterior vertebral wall defect group. However, there were significant differences with respect to the incidence of bone cement leakage among the posterior wall defect groups. In four groups the postoperative VAS pain scores and KPS were statistical different as comparison to the preoperative values. No statistical difference with respect to the VAS pain scores and KPS was observed at any time point between the non-posterior wall defect group and posterior wall defect group. CONCLUSION: PVP can be an effective treatment for metastatic spinal tumors in patients with posterior wall deficiency; however, care should be taken to control the distribution of the bone cement due to the relatively high risk of cement leakage.

Status and prospects of percutaneous vertebroplasty combined with ¹²5I seed implantation for the treatment of spinal metastases.

Metastatic spinal tumours are the most common type of bone metastasis. Various methods have been used to treat metastatic spinal lesions, including radiotherapy, chemotherapy, isotope therapy, bisphosphonate therapy, analgesics, and surgery. Conservative treatments such as radiotherapy and chemotherapy are not appropriate and usually are ineffective in patients with vertebral fractures and/or spinal instability. Minimally invasive surgical treatments using non-vascular interventional technology, such as percutaneous vertebroplasty (PVP), have been successfully performed in the clinical setting. PVP is a non-invasive procedure that creates small wounds and is usually associated with only minor complications. In the present study, we will review the clinical status and prospects for the use PVP combined with (125)I seed implantation (PVPI) to treat spinal metastases. The scientific evidence for this treatment, including safety, efficacy, and outcome measures, as well as comparisons with other therapies, was analysed in detail. PVPI effectively alleviates pain in metastatic spinal tumour patients, and the use of interstitial (125)I seed implants can enhance the clinical outcomes. In conclusion, PVPI is a safe, reliable, effective, and minimally invasive treatment. The techniques of PVP and (125)I seed implantation complement each other and strengthen the treatment's effect, presenting a new alternative treatment for spinal metastases with potentially wide application.

Minimal access versus open spinal surgery in treating painful spine metastasis: a systematic review.

STUDY DESIGN: The study design of this paper is a systematic review of literature published in the recent 10 years. OBJECTIVE: It is the objective of this paper to compare the clinical efficacy and safety of minimal access (MIS) spinal surgery and open spinal surgery for treating painful spine metastasis. METHODS: Two research questions below were determined through a consensus among a panel of spine experts. A systematic review of literature on spinal surgery was conducted by searching PubMed with a combination of keywords including "metastatic", "metastasis", "metastases", "spinal", and "spine". Independent reviewers selected the articles for analysis after screening the titles, abstracts, and full texts, then extracted data and graded the quality of each paper according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria. Specific clinical questions were as follows: 1. In patients with spine metastatic disease, what is the impact of different surgical approaches (MIS versus open) on pain relief and functional outcome? 2. In patients with metastatic disease, what is the impact of different surgical approaches (MIS versus open) on local recurrence, survive rate, and complication? RESULTS: A total of 1,076 abstracts were identified using various keywords. 5 prospective (level II) and 12 retrospective articles (level III) were eligible for inclusion, involving a total of 979 cases of spine metastasis. There were 345 cases in 8 studies regarding the clinical evaluation of MIS spinal surgery and 634 cases in 9 studies regarding the clinical evaluation of open spinal surgery for spine metastasis. CONCLUSION: Both open spinal surgery and MIS seem to achieve the improvement of pain and neurological dysfunction through decompression and stabilization for patients with spine metastasis, but open surgery may involve more major complications with a trend of lower survival rates and higher recurrence rates compared to MIS.

Expression of ezrin, CD44, and VEGF in giant cell tumor of bone and its significance.

BACKGROUND: This research aimed to study the role of ezrin, CD44, and VEGF in invasion, metastasis, recurrence, and prognosis of giant cell tumor of bone (GCTB) and its association with the clinical and pathological features of GCTB. METHODS: Expression status of ezrin, CD44, and VEGF in 80 GCTB tissues and its adjacent noncancerous tissue samples were measured with immunohistochemical and Elivison staining. Their correlation with the clinical and pathologic factors was statistically analyzed by chi-square test. RESULTS: The expression status of ezrin, CD44, and VEGF were significantly higher in GCTB tissue samples than in its adjacent noncancerous tissue samples and in GCTB at Campanacci stage III than in Campanacci stages I and II (P < 0.05). No significant difference was found in age and sex of the patients and locations of the tumor (P > 0.05). Survival analysis showed that the expression status of ezrin, CD44, VEGF, and Campanacci clinical stages of GCTB were positively associated with the survival rate of GCTB patients and negatively associated with ezrin and Campanacci stages of GCTB, indicating that ezrin, CD44, VEGF, and Campanacci clinical stages of GCTB are the independent factors for GCTB. CONCLUSIONS: Ezrin, CD44, and VEGF are over-expressed in GCTB tissue and its adjacent noncancerous tissue samples and may play an important role in the occurrence, invasion, metastasis, and recurrence of GCTB. Measurement of ezrin, CD44, and VEGF expression status may contribute to the judgment of prognosis of GCTB patients.

Meta-analysis of differentially expressed genes in osteosarcoma based on gene expression data.

BACKGROUND: To uncover the genes involved in the development of osteosarcoma (OS), we performed a meta-analysis of OS microarray data to identify differentially expressed genes (DEGs) and biological functions associated with gene expression changes between OS and normal control (NC) tissues. METHODS: We used publicly available GEO datasets of OS to perform a meta-analysis. We performed Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Protein-Protein interaction (PPI) networks analysis. RESULTS: Eight GEO datasets, including 240 samples of OS and 35 samples of controls, were available for the meta-analysis. We identified 979 DEGs across the studies between OS and NC tissues (472 up-regulated and 507 down-regulated). We found GO terms for molecular functions significantly enriched in protein binding (GO: 0005515, P = 3.83E-60) and calcium ion binding (GO: 0005509, P = 3.79E-13), while for biological processes, the enriched GO terms were cell adhesion (GO:0007155, P = 2.26E-19) and negative regulation of apoptotic process (GO: 0043066, P = 3.24E-15), and for cellular component, the enriched GO terms were cytoplasm (GO: 0005737, P = 9.18E-63) and extracellular region (GO: 0005576, P = 2.28E-47). The most significant pathway in our KEGG analysis was Focal adhesion (P = 5.70E-15). Furthermore, ECM-receptor interaction (P = 1.27E-13) and Cell cycle (P = 4.53E-11) are found to be highly enriched. PPI network analysis indicated that the significant hub proteins containing PTBP2 (Degree = 33), RGS4 (Degree = 15) and FXYD6 (Degree = 13). CONCLUSIONS: Our meta-analysis detected DEGs and biological functions associated with gene expression changes between OS and NC tissues, guiding further identification and treatment for OS.

Interaction of ncRNAs and the PI3K/AKT/mTOR pathway: Implications for osteosarcoma.

Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents, and is characterized by high heterogeneity, high malignancy, easy metastasis, and poor prognosis. Recurrence, metastasis, and multidrug resistance are the main problems that limit the therapeutic effect and prognosis of OS. PI3K/AKT/mTOR signaling pathway is often abnormally activated in OS tissues and cells, which promotes the rapid development, metastasis, and drug sensitivity of OS. Emerging evidence has revealed new insights into tumorigenesis through the interaction between the PI3K/AKT/mTOR pathway and non-coding RNAs (ncRNAs). Therefore, we reviewed the interactions between the PI3K/AKT/mTOR pathway and ncRNAs and their implication in OS. These interactions have the potential to serve as cancer biomarkers and therapeutic targets in clinical applications.

Percutaneous vertebroplasty combined with interstitial implantation of 125I seeds in banna mini-pigs.

BACKGROUND: Although brachytherapy is one of the most effective ways to treat metastatic spinal tumor with little damage to surrounding healthy tissue, it may cause radiation myelopathy if an overdose occurs. Establishing a valuable animal model can help to find a method to overcome its complications. In the current study, we set up a banna mini-pig model to mimic percutaneous vertebroplasty with 125I seed implantation. METHODS: Percutaneous vertebroplasty (PVP) combined with interstitial implantation of 125I seeds, 125I seeds were transplanted into the vertebral body at the T13 level of the spine in banna mini-pigs. After raising them for up to eight months, the spinal cord and vertebral body were collected for pathological analysis. RESULTS: A potential animal model had been successfully established, no case of radiation myelopathy was found in any of the treated banna pigs, and no significant cellular impairment was noted by pathological analysis. CONCLUSIONS: It proves that PVP with 125I brachytherapy is an effective method to treat metastasis spinal tumor, and that the banna mini-pig can be a suitable model to investigate the mechanism of brachytherapy complications.

Low-dose aspirin can inhibit exosomal release induced by radiotherapy in breast cancer and attenuate its inhibitory effect on NK cell proliferation.

BACKGROUND: Breast cancer (BC) seriously threatens women's health. Aspirin plays a key role in the treatment and prognosis of BC. OBJECTIVE: To explore the effect of low-dose aspirin on BC radiotherapy through the mechanism of exosomes and natural killer (NK) cells. METHODS: BC cells were injected into the left chest wall to establish a BC model in nude mice. Tumor morphology and size were observed. Immunohistochemical staining for Ki-67 was used to observe the proliferation of tumor cells. TUNEL was used to detect the apoptosis of cancer cells. Protein levels of exosomal biogenesis- and secretion-related genes (Rab 11, Rab27a, Rab27b, CD63, and Alix) were detected by Western blot. Flow cytometry was used to detect apoptosis. Transwell assays were used to detect cell migration. A clonogenic assay was used to detect cell proliferation. Exosomes of BT549 and 4T1-Luc cells were extracted and observed by electron microscopy. After the coculture of exosomes and NK cells, the activity of NK cells was detected by CCK-8. RESULTS: The protein expression of genes related to exosomal genesis and secretion (Rab 11, Rab27a, Rab27b, CD63, and Alix) in BT549 and 4T1-Luc cells was upregulated under radiotherapy treatment. Low doses of aspirin inhibited exosome release from BT549 and 4T1-Luc cells and alleviated the inhibitory effect of BC cell exosomes on NK cell proliferation. In addition, knocking down Rab27a reduced the protein levels of exosome-related and secretion-related genes in BC cells, further enhancing the promotive effect of aspirin on NK cell proliferation, while overexpressing Rab27a had the opposite effect. Aspirin was combined at a radiotherapeutic dose of 10 Gy to enhance the radiotherapy sensitivity of radiotherapy-tolerant BC cells (BT549R and 4T1-LucR). Animal experiments have also verified that aspirin can promote the killing effect of radiotherapy on cancer cells and significantly inhibit tumor growth. CONCLUSION: Low doses of aspirin can inhibit the release of BC exosomes induced by radiotherapy and weaken their inhibition of NK cell proliferation, promoting radiotherapy resistance.

The potential role of m6A reader YTHDF1 as diagnostic biomarker and the signaling pathways in tumorigenesis and metastasis in pan-cancer.

m6A is an important RNA methylation in progression of various human cancers. As the m6A reader protein, YTHDF1 is reported to accelerate m6A-modified mRNAs translation in cytoplasm. It is highly expressed in various human cancers and contributes to the progression and metastasis of cancers. YTHDF1 was closely associated with poor prognosis and also used as a molecular marker for clinical diagnosis or therapy in human cancers. It has been reported to promote chemoresistance to Adriamycin, Cisplatin and Olaparib by increasing mRNA stability of its target molecule. Moreover, it contributes to CSC-like characteristic of tumor cells and inducing the antitumor immune microenvironment. Here, we reviewed the clinical diagnostic and prognostic values of YTHDF1, as well as the molecular mechanisms of YTHDF1 in progression and metastasis of human cancers.

miR-137-LAPTM4B regulates cytoskeleton organization and cancer metastasis via the RhoA-LIMK-Cofilin pathway in osteosarcoma.

Osteosarcoma (OS) is a rare malignant bone tumor but is one leading cause of cancer mortality in childhood and adolescence. Cancer metastasis accounts for the primary reason for treatment failure in OS patients. The dynamic organization of the cytoskeleton is fundamental for cell motility, migration, and cancer metastasis. Lysosome Associated Protein Transmembrane 4B (LAPTM4B) is an oncogene participating in various biological progress central to cancer biogenesis. However, the potential roles of LAPTM4B in OS and the related mechanisms remain unknown. Here, we established the elevated LAPTM4B expression in OS, and it is essential in regulating stress fiber organization through RhoA-LIMK-cofilin signaling pathway. In terms of mechanism, our data revealed that LAPTM4B promotes RhoA protein stability by suppressing the ubiquitin-mediated proteasome degradation pathway. Moreover, our data show that miR-137, rather than gene copy number and methylation status, contributes to the upregulation of LAPTM4B in OS. We report that miR-137 is capable of regulating stress fiber arrangement, OS cell migration, and metastasis via targeting LAPTM4B. Combining results from cells, patients' tissue samples, the animal model, and cancer databases, this study further suggests that the miR-137-LAPTM4B axis represents a clinically relevant pathway in OS progression and a viable target for novel therapeutics.

Treatment of MM-associated spinal fracture with percutaneous vertebroplasty (PVP) and chemotherapy.

PURPOSE: To investigate the effect of treatment of multiple myeloma (MM)-associated spinal fracture with percutaneous vertebroplasty (PVP) and chemotherapy. METHODS: Patients with MM-associated spinal fracture were randomly divided into combined (PVP and chemotherapy) treatment group (n = 38) and single chemotherapy group (n = 38). For the combined treatment group, bone cement was injected into vertebral body via DSA guided-percutaneous puncture. M2 scheme was used for both groups. And a 5-year follow-up was conducted for the study. RESULTS: At the 1-year follow-up visits, PVP combined with chemotherapy achieved complete remission (CR) in six patients (15.8%); near complete remission (nCR) in ten patients (26.30%); partial remission (PR) in nine patients (23.7%); minimal response (MR) in three patients (7.9%); no change (NC) in four patients (10.5%), and disease progression (DP) in five patients (13.2%). Only chemotherapy alone resulted in 3 CR (7.9%); 8 nCR (26.30%); 19 PR (77.5%); 4 MR (17.5%); 4 NC (17.5%), and 2 DP (5.0%). While the overall response rate (ORR) in the combined treatment group (65.8%) and the single chemotherapy group (50.0%) were significantly different, their visual analog pain scales (3.01 ± 0.62 and 5.97 ± 0.40, respectively) and Karnofsky performance scores (89.4 ± 6.3 and 80.3 ± 7.2, respectively) were significantly improved after treatment (P = 0.032 and P = 0.002, respectively). And the ORR between the two groups were significantly different (P = 0.001). CONCLUSION: Percutaneous vertebroplasty is a minimally invasive surgery for MM-associated pathologic fracture. PVP had the characteristics of minimal trauma, easy operation and less complication. PVP can achieve long-term analgesic effect, and enhance the spinal stability.

Study of treatment using percutaneous acetabuloplasty and interstitial implantation of (125)I seeds for patients with metastatic periacetabular tumors.

BACKGROUND: The periacetabular area is one of the primary sites of metastatic tumors, which often present as osteolytic bone destruction. Bone destruction in the acetabulum caused by metastatic tumors will cause hip pain and joint dysfunction. It results in decreased quality of life for patients. The aim of our study was to explore the clinical effect of metastatic periacetabular tumors treated with percutaneous cementoplasty and interstitial implantation of (125)I seeds. METHODS: A retrospective analysis was performed on 24 patients with metastatic periacetabular tumors who underwent combined therapy of percutaneous acetabuloplasty and interstitial implantation of (125)I seeds between February 2003 and June 2011. There were 13 males and 11 females aged 19-80 years with a mean age of 57.3. The primary tumor site was the lung in eight cases, the breast in six, the prostate cancer in eight, and the liver in two. The amount of implanted (125)I seeds was 12-20 seeds/person, with a mean of 16.5 seeds/person, and the matching peripheral dosage (MPD) was 80~100Gy. Routine postoperative chemotherapy and other combined treatments were applied to patients after the surgical operation. Changes in the Karnofsky Score(KPS), Harris Hip Score(Harris), and Visual Analog Scale(VAS) were observed during the follow-up period. RESULTS: The 24 patients' operations were all successful. No major complications occurred. Complete pain relief was achieved in 58% (14 of 24) of patients, and pain reduction was achieved in the 42% remaining (10) patients. The mean duration of pain relief was 8.3 months. Pain recurred in one patient 3 months after surgery. Six patients had died and 18 patients were alive at the time of the 1-year follow-up. Comparing the KPS, Harris and VAS scores pre- and postoperativelyat 1, 6, and 12 months, the combined therapy method was significantly effective in metastatic periacetabular tumor patients (P<0.05). CONCLUSIONS: Percutaneous cementoplasty with interstitial implantation of (125)I seeds is an effective treatment method for metastatic periacetabular tumor patients, providing tumor resistance, pain relief, increased bone stability, and improved quality of life for patients.

Pathological impairments induced by interstitial implantation of 125I seeds in spinal canal of banna mini-pigs.

BACKGROUND: Use a banna mini-pig to set up 125I implantation model, and investigate the consequence of radiation-related impairments. METHODS: In present study, 125I seeds were implanted into spinal canal of T13 level of spine in banna mini-pigs. After operation, the pigs were raised up to 8 months, behavior changes were recorded within this period. After 8 months, spinal cords were collected for pathological analysis. RESULTS: In this study, a 125I brachytherapy animal model had been successfully established, in the model group, the banna pigs' Tarlov scale decreased from 5 to 2.57 ± 0.36, significant cellular impairments were noted by pathological analysis. CONCLUSIONS: Without any protection and operation improvement, 125I implantation can cause serious histological impairments and moving difficulty for banna mini-pigs; this present research provides an alternative tool to study spinal 125I brachytherapy.

Mouse mesenchymal stem cell-derived exosomal miR-466f-3p reverses EMT process through inhibiting AKT/GSK3ß pathway via c-MET in radiation-induced lung injury.

BACKGROUND: Radiation-induced lung fibrosis (RILF) is a common complication of thoracic radiotherapy. Alveolar epithelial cells play a crucial role in lung fibrosis via epithelial-mesenchymal transition (EMT). Exosomes derived from mesenchymal stem cells own the beneficial properties to repair and regeneration of damaged tissues, however the underlying mechanisms remain poorly understood. METHODS: Mouse mesenchymal stem cells-derived exosomes (mMSCs-Exo) were isolated by differential centrifugation, and their protective effects were assessed in vivo and in vitro, respectively. EMT-associated proteins were measured via western blot assay and/or immunofluorescence staining. The miRNA expression was measured by microarray assay and qPCR. Furthermore, bioinformatics prediction with KEGG analysis, luciferase assay, and rescue experiments were performed to explore the molecular mechanism underlying miR-466f-3p. RESULTS: mMSCs-Exos were efficiently isolated ranging from 90-150 nm with high expression of exosomal markers (CD63, TSG101, and CD9). mMSCs-Exos administration efficiently relieved radiation-induced lung injury with less collagen deposition and lower levels of IL-1ß and IL-6. Meanwhile, in vitro results showed mMSCs-Exos treatment obviously reversed EMT process induced by radiation. Among enriched miRNA cargo in exosomes, miR-466f-3p was primarily responsible for the protective effects via inhibition of AKT/GSK3ß pathway. Our mechanistic study further demonstrated that c-MET was the direct target of miR-466f-3p, whose restoration partially abrogated mMSCs-Exo-mediated inhibition in both EMT process and AKT/GSK3ß signaling activity induced by radiation. CONCLUSIONS: Our findings indicated that exosomal miR-466f-3p derived from mMSCs may possess anti-fibrotic properties and prevent radiation-induced EMT through inhibition of AKT/GSK3ß via c-MET, providing a promising therapeutic modality for radiation-induced lung fibrosis.