Osteosarcoma-targeted Cu and Ce based oxide nanoplatform for NIR II fluorescence/magnetic resonance dual-mode imaging and ros cascade amplification along with immunotherapy.

BACKGROUND: As the lethal bone tumor, osteosarcoma often frequently occurs in children and adolescents with locally destructive and high metastasis. Distinctive kinds of nanoplatform with high therapeutical effect and precise diagnosis for osteosarcoma are urgently required. Multimodal optical imaging and programmed treatment, including synergistic photothermal-chemodynamic therapy (PTT-CDT) elicits immunogenetic cell death (ICD) is a promising strategy that possesses high bio-imaging sensitivity for accurate osteosarcoma delineating as well as appreciable therapeutic efficacy with ignorable side-effects. METHODS AND RESULTS: In this study, mesoporous Cu and Ce based oxide nanoplatform with Arg-Gly-Asp (RGD) anchoring is designed and successfully constructed. After loading with indocyanine green, this nanoplatform can be utilized for precisely targeting and efficaciously ablating against osteosarcoma via PTT boosted CDT and the closely following ICD stimulation both in vitro and in vivo. Besides, it provides off-peak fluorescence bio-imaging in the second window of near-infrared region (NIR II, 1000-1700 nm) and Magnetic resonance signal, serves as the dual-mode contrast agents for osteosarcoma tissue discrimination. CONCLUSION: Tumor targeted Cu&Ce based mesoporous nanoplatform permits efficient osteosarcoma suppression and dual-mode bio-imaging that opens new possibility for effectively diagnosing and inhibiting the clinical malignant osteosarcoma.

Prediction of nonsentinel lymph node metastasis in acral melanoma with positive sentinel lymph nodes.

BACKGROUND: Metastasis in a nonsentinel lymph node (non-SLN) is an unfavorable independent prognostic factor in cutaneous melanoma (CM). Recent data did suggest potential value of completion lymph node dissection (CLND) in CM patients with non-SLN metastasis. Prediction of non-SLN metastasis assists clinicians in deciding on adjuvant therapy without CLND. We analyzed risk factors and developed a prediction model for non-SLN status in acral melanoma (AM). METHODS: This retrospective study enrolled 656 cases of melanoma who underwent sentinel lymph node biopsy at Fudan University Shanghai Cancer Center from 2009 to 2017. We identified 81 SLN + AM patients who underwent CLND. Clinicopathologic data, including SLN tumor burden and non-SLN status were examined with Cox and Logistics regression models. RESULTS: Ulceration, Clark level, number of deposits in the SLN (NumDep) and maximum size of deposits (MaxSize) are independent risk factors associated with non-SLN metastases. We developed a scoring system that combines ulceration, the cutoff values of Clark level V, MaxSize of 2 mm, and NumDep of 5 to predict non-SLN metastasis with an efficiency of 85.2% and 100% positive predictive value in the high-rank group (scores of 17-24). CONCLUSIONS: A scoring system that included ulceration, Clark level, MaxSize, and NumDep is reliable and effective for predicting non-SLN metastasis in SLN-positive AM.

Optimal timing of re-excision in synovial sarcoma patients: Immediate intervention versus waiting for local recurrence.

BACKGROUND: To investigate the difference in efficacy of re-excision in synovial sarcoma patients with and without residual tumor following unplanned excision, and to compare the prognostic outcomes of immediate re-excision versus waiting for local recurrence. METHOD: This study included synovial sarcoma patients who underwent re-excision at our center between 2009 and 2019, categorized into groups based on unplanned excision and local recurrence. Analyzed endpoints included overall survival (OS), local recurrence-free survival (LRFS), and distant relapse-free survival (DRFS). Prognostic factors associated with these three different survival outcomes were analyzed through the use of Kaplan-Meier curves and Cox regression approaches. RESULT: In total, this study incorporated 109 synovial sarcoma patients, including 32 (29.4%) with no residual tumor tissue identified after re-excision, 31 (28.4%) with residual tumor tissue after re-excision, and 46 (42.2%) with local recurrence after initial excision. Patients were assessed over a median 52-month follow-up period. The respective 5-year OS, 5-year LRFS, and 5-year DRFS rates were 82.4%, 76.7%, and 74.2% for the nonresidual group, 80.6%, 80.4%, and 77.3% for the residual tumor tissue group, and 63.5%, 50.7%, and 46.3% for the local recurrence group. There was no significant difference in OS of nonresidual group and residual group patients after re-excision (p = 0.471). Concurrent or sequential treatment with chemotherapy and radiotherapy significantly reduced the risk of metastasis and mortality when compared with noncombined chemoradiotherapy, and was more effective in the local recurrence group (p < 0.05). CONCLUSION: Prompt and adequate re-excision is crucial for patients with synovial sarcoma who undergo initial inadequate tumor excision, and their prognosis is significantly better compared with patients who delay re-excision until local recurrence.

Does primary tumor resection improve survival for patients with sarcomas of pelvic bones, sacrum, and coccyx who have metastasis at diagnosis ?

BACKGROUND: Recent studies demonstrated that primary tumor resection (PTR) improves survival of patients with metastatic bone sarcomas. However, it remains quite unclear regarding the role of PTR in the treatment of sarcomas of pelvic bones with synchronous metastasis at diagnosis. METHODS: Using the Surveillance, Epidemiology, and End Results Program, we enrolled a total of 385 patients with sarcomas of pelvic bones, sacrum, and coccyx who have metastasis at initial diagnosis, including 139 patients with osteosarcoma, 176 with Ewing sarcoma, and 70 with chondrosarcoma. Association between PTR and disease-specific survival (DSS) were investigated using the univariable and multivariable Cox regression models. Hazard ratio (HR) and 95% confidence interval (CI) were reported. Representative institutional PTR strategies and clinical outcomes for patients with metastatic pelvic sarcomas from our cancer center were displayed. RESULTS: The usage rate of PTR was 28.1% (39/139) in osteosarcoma, 13.6% (24/176) in Ewing sarcoma, and 41.4% (29/70) in chondrosarcoma with synchronous metastatic lesions. PTR was not associated with an improved DSS for metastatic pelvic osteosarcoma (HR = 0.686, 95% CI = 0.430 ~ 1.094, P = 0.113) and Ewing sarcoma (HR = 0.580, 95% CI = 0.291 ~ 1.154, P = 0.121). The use of PTR was associated with an improved DSS for metastatic pelvic chondrosarcoma (HR = 0.464, 95% CI = 0.225 ~ 0.954, P = 0.037). CONCLUSION: Primary lesion resection may provide a survival benefit for metastatic chondrosarcoma, but not for osteosarcoma and Ewing sarcoma of pelvic bones, sacrum, and coccyx. This population-based study recommends an active surgical intervention for metastatic chondrosarcoma while non-surgical treatment for metastatic osteosarcoma and Ewing sarcoma of the pelvis in terms of survival improvement.

Head-to-head evaluation of [18F]FDG and [68 Ga]Ga-DOTA-FAPI-04 PET/CT in recurrent soft tissue sarcoma.

PURPOSE: We aimed to evaluate the value of [68 Ga]Ga-DOTA-FAPI-04 PET/CT for the diagnosis of recurrent soft tissue sarcoma (STS), compared with [18F]FDG PET/CT. METHODS: A total of 45 patients (21 females and 24 males; median age, 46 years; range, 18-71 years) with 13 subtypes of STS underwent [18F]FDG and [68 Ga]Ga-DOTA-FAPI-04 PET/CT examination within 1 week for assessment local relapse or distant metastasis. Positive lesions on PET/CT images were verified by biopsy or 3-month follow-up. Wilcoxon matched-pairs signed-rank test was used to compare the semiquantitative values (SUVmax and TBR) of [18F]FDG and [68 Ga]Ga-DOTA-FAPI-04 in tumor lesions, and McNemar test was applied to test for differences of both tracers. RESULTS: Among the 45 patients, 282 local relapses and distant metastases were identified. Compared to [18F]FDG, [68 Ga]Ga-DOTA-FAPI-04 PET/CT detected more lesions (275 vs. 186) and outperformed in sensitivity, specificity, PPV, NPV, and accuracy for the diagnosis of recurrent lesions (P < 0.001). [68 Ga]Ga-DOTA-FAPI-04 demonstrated significantly higher values of SUVmax and TBR than [18F]FDG PET/CT in liposarcoma (P = 0.011 and P < 0.001, respectively), malignant solitary fibrous tumor (MSFT) (P < 0.001 and P < 0.001, respectively), and interdigitating dendritic cell sarcoma (IDCS) (P < 0.001and P < 0.001, respectively). While mean SUVmax and TBR presented favorable uptake of [18F]FDG over [68 Ga]Ga-DOTA-FAPI-04 in undifferentiated pleomorphic sarcoma (UPS) (P = 0.003 and P < 0.001, respectively) and rhabdomyosarcoma (RMS) (P < 0.001 and P < 0.001, respectively). CONCLUSION: [68 Ga]Ga-DOTA-FAPI-04 PET/CT is a promising new imaging modality for recurrent surveillance of STS, and compares favorably with [18F]FDG for identifying recurrent lesions of liposarcoma, MSFT, and IDCS.

BRAF Inhibitor Resistance in Melanoma: Mechanisms and Alternative Therapeutic Strategies.

OPINION STATEMENT: Melanoma is caused by a variety of somatic mutations, and among these mutations, BRAF mutation occurs most frequently and has routinely been evaluated as a critical diagnostic biomarker in clinical practice. The introduction of targeted agents for BRAF-mutant melanoma has significantly improved overall survival in a large proportion of patients. However, there is BRAF inhibitor resistance in most patients, and its mechanisms are complicated and need further clarification. Additionally, treatment approaches to overcome resistance have evolved rapidly, shifting from monotherapy to multimodality treatment, which has dramatically improved patient outcomes in clinical trials and practice. This review highlights the mechanisms of BRAF inhibitor resistance in melanoma and discusses the current state of its therapeutic approaches that can be further explored in clinical practice.

Burn-induced heterotopic ossification from incidence to therapy: key signaling pathways underlying ectopic bone formation.

Burn injury is one of the potential causes of heterotopic ossification (HO), which is a rare but debilitating condition. The incidence ranges from 3.5 to 5.6 depending on body area. Burns that cover a larger percentage of the total body surface area (TBSA), require skin graft surgeries, or necessitate pulmonary intensive care are well-researched risk factors for HO. Since burns initiate such complex pathophysiological processes with a variety of molecular signal changes, it is essential to focus on HO in the specific context of burn injury to define best practices for its treatment. There are numerous key players in the pathways of burn-induced HO, including neutrophils, monocytes, transforming growth factor-ß1-expressing macrophages and the adaptive immune system. The increased inflammation associated with burn injuries is also associated with pathway activation. Neurological and calcium-related contributions are also known. Endothelial-to-mesenchymal transition (EMT) and vascularization are known to play key roles in burn-induced HO, with hypoxia-inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) as potential initiators. Currently, non-steroidal anti-inflammatory drugs (NSAIDs) and radiotherapy are effective prophylaxes for HO. Limited joint motion, ankylosis and intolerable pain caused by burn-induced HO can be effectively tackled via surgery. Effective biomarkers for monitoring burn-induced HO occurrence and bio-prophylactic and bio-therapeutic strategies should be actively developed in the future.

Potential protective mechanisms of green tea polyphenol EGCG against COVID-19.

BACKGROUND: The world is in the midst of the COVID-19 pandemic. In this comprehensive review, we discuss the potential protective effects of (-)-epigallocatechin-3-gallate (EGCG), a major constituent of green tea, against COVID-19. SCOPE AND APPROACH: Information from literature of clinical symptoms and molecular pathology of COVID-19 as well as relevant publications in which EGCG shows potential protective activities against COVID-19 is integrated and evaluated. KEY FINDINGS AND CONCLUSIONS: EGCG, via activating Nrf2, can suppress ACE2 (a cellular receptor for SARS-CoV-2) and TMPRSS2, which mediate cell entry of the virus. Through inhibition of SARS-CoV-2 main protease, EGCG may inhibit viral reproduction. EGCG via its broad antioxidant activity may protect against SARS-CoV-2 evoked mitochondrial ROS (which promote SARS-CoV-2 replication) and against ROS burst inflicted by neutrophil extracellular traps. By suppressing ER-resident GRP78 activity and expression, EGCG can potentially inhibit SARS-CoV-2 life cycle. EGCG also shows protective effects against 1) cytokine storm-associated acute lung injury/acute respiratory distress syndrome, 2) thrombosis via suppressing tissue factors and activating platelets, 3) sepsis by inactivating redox-sensitive HMGB1, and 4) lung fibrosis through augmenting Nrf2 and suppressing NF-κB. These activities remain to be further substantiated in animals and humans. The possible concerted actions of EGCG suggest the importance of further studies on the prevention and treatment of COVID-19 in humans. These results also call for epidemiological studies on potential preventive effects of green tea drinking on COVID-19.

Correction to: microRNA-124 inhibits bone metastasis of breast cancer by repressing Interleukin-11.

An amendment to this paper has been published and can be accessed via the original article.

Retracted: Naturally Occurring Sesquiterpene Lactone-Santonin, Exerts Anticancer Effects in Multi-Drug Resistant Breast Cancer Cells by Inducing Mitochondrial Mediated Apoptosis, Caspase Activation, Cell Cycle Arrest, and by Targeting Ras/Raf/MEK/ERK Signaling Pathway.

It is now clear that the photomicrographs in Figure 2 are duplicates of the same image and that Figures 4 and 5 have been 'copied' from a publication "Lupeol triterpene exhibits potent antitumor effects in A427 human lung carcinoma cells via mitochondrial mediated apoptosis, ROS generation, loss of mitochondrial membrane potential and downregulation of m-TOR/PI3Ksol;AKT signalling pathway" by Wei He, Xiang Li, Shuyue Xia, PMID: 30003730. Because the manuscript contains non-credible results and has also breached copyright, this journal is retracting the above publication.

Outcome of patients with primary retroperitoneal solitary fibrous sarcoma.

BACKGROUND: To describe the clinicopathological features of primary retroperitoneal solitary fibrous tumor (RSFT) and define the prognostic factors. METHODS: The comprehensive data of 35 primary RSFT patients who got curative surgery at a tertiary cancer center from April 2004 to October 2018 were retrospectively analyzed. RESULTS: Male patients outnumbered female patients (19 vs. 16), with the age ranging from 19 to 73 years (median, 51 years). 7 (20%) patients had tumors located in special parts, including three in kidney, one in renal pelvis, one in bladder, one in prostate, and one in mesentery. Tumor sizes ranged from 2.5 to 25 cm (median, 9 cm). Microscopic negative margin was reached in 33 (94.3%) cases. 13 (37.1%) were classified as atypical/malignant, while 22 (62.9%) were benign. Concomitant organ excision was performed on 11 (31.4%) patients, with kidney (n = 5) being the most frequent organ. Multifocality was only found in 4 (11.4%) cases. The majority of the patients (31, 88.6%) did not get adjuvant treatment. The median follow-up time was 46 months (range 4-153 months). The 5-year DSS rate and DFS rate were 100% and 63.6%, respectively. In univariate analysis, tumor size ≥ 10 cm (P = 0.002) and atypical/malignant pathology (P = 0.024) were associated with decreased DFS. Multivariate analysis revealed that tumor size was the only independent prognostic factor for DFS (HR 6.03, 95% CI 1.18-30.77, P = 0.031). CONCLUSION: RSFT is uncommon, slow-growing, and recrudescent tumors. Large tumor size and malignant pathology are associated with decreased DFS. Tumor size ≥ 10 cm independently predicts shortened DFS.

Knockdown of Kinesin Family 15 Inhibits Osteosarcoma through Suppressing Cell Proliferation and Promoting Cell Apoptosis.

Kinesin family (KIF) members have vital roles in mitosis, meiosis, and transport of macromolecules in eukaryotic cells. In this study, we aimed to investigate the role of KIF15 in osteosarcoma. Immunohistochemical staining was performed to determine expression levels of KIF15 in osteosarcoma tissues and adjacent normal tissues. Tissue microarray analysis showed a correlation between the expression of KIF15 and pathological features of patients. Subsequently, lentivirus was used to inhibit the expression of KIF15 in osteosarcoma cells. An MTT assay was performed to examine cell proliferation. Transwell and wound healing assays were used to estimate the invasion and migration of osteosarcoma cells, respectively. Flow cytometric analysis was employed to define the apoptosis of osteosarcoma cells. Our results showed that KIF15 expression was significantly upregulated in osteosarcoma tissues compared with adjacent normal tissues. The Mann-Whitney U test and Spearman correlation analysis showed that the expression levels of KIF15 in osteosarcoma tissues were positively correlated with tumor infiltrate, a pathological characteristic of patients. The expression of KIF15 was successfully suppressed by shKIF15, and the knockdown efficiency reached 80 and 69% in MNNG/HOS and U2OS cells, respectively. Subsequently, knockdown of KIF15 significantly inhibited the capacity of cell proliferation, colony formation, invasion, and migration, but enhanced G2 phase arrest and partially enhanced cell apoptosis. This study preliminarily showed KIF15 to be a critical regulatory molecule involved in osteosarcoma cell proliferation. Consequently, KIF15 can be a potential diagnostic and therapeutic target for osteosarcoma.

Naturally Occurring Sesquiterpene Lactone-Santonin, Exerts Anticancer Effects in Multi-Drug Resistant Breast Cancer Cells by Inducing Mitochondrial Mediated Apoptosis, Caspase Activation, Cell Cycle Arrest, and by Targeting Ras/Raf/MEK/ERK Signaling Pathway.

BACKGROUND Sesquiterpene lactones have gained tremendous attention owing to their potent anticancer properties. The main focus of this study was to evaluate the anticancer effects of a naturally occurring sesquiterpene lactone, santonin, against human breast cancer SK-BR-3 cells. MATERIAL AND METHODS Cell counting kit 8 assay was used for the determination of cell viability. Apoptosis was detected by DAPI (4',6-diamidino-2-phenylindole) and annexin V/propidium iodide (IP) staining. Flow cytometry was used for cell cycle analysis and western blotting was used for the estimation of protein expression. RESULTS Results showed that santonin exerts significant anti-proliferative effects on the SK-BR-3 breast cancer cells in a concentration dependent manner. Santonin showed an IC50 of 16 µM against SK-BR-3 cells. DAPI staining showed that santonin caused DNA fragmentation in the SK-BR-3 cells, which is indicative of apoptosis. Annexin V/PI staining showed that apoptotic cell percentage increased up to 34.32% at 32 µM concentration of santonin. Santonin also caused an increase in the expression of Bax, caspase-3, and caspase-9, and a decrease in the expression of Bcl-2. Santonin also caused the arrest of the SK-BR-3 cells at the G2/M phase of the cell cycle and suppressed the expression of cyclin A and B1. Finally, santonin could also block the Raf/MEK/ERK pathway in breast cancer cells. CONCLUSIONS The findings of this study suggest the potential for the naturally occurring sesquiterpene lactone santonin in breast cancer treatment and also suggest that it could be developed as a promising anticancer agent.

Prognostic analysis of surgically treated clear cell sarcoma: an analysis of a rare tumor from a single center.

BACKGROUND: The objective of this retrospective study was to evaluate the prognostic value of various factors in clear cell sarcoma patients after radical surgery. METHODS: Forty-two clear cell sarcoma patients from August 2006 to March 2018 were included in the study. Curves of disease-free survival and overall survival were calculated using the Kaplan-Meier method, and univariate and multivariate analyses of various prognostic factors were performed using a Cox proportional hazard regression model. Laboratory test of peripheral blood was recorded before surgery. The optimal cutoff value of systemic inflammatory markers was defined by receiver-operating curve analysis. RESULTS: The 5-year DFS and 5-year OS rate were 22% and 46%, respectively. The median DFS and OS times were 12 and 41.5 months, respectively. In univariate analysis, there was a significant association between shorter DFS and tumor size larger than 5 cm (p = 0.0043), positive surgical margin (p = 0.0233), and the neutrophil-to-lymphocyte ratio (NLR) higher than 2.73 (p = 0.0009). Furthermore, we observed a significant association between shorter OS and tumor size larger than 5 cm (p = 0.0075), positive surgical margin (p = 0.0101), NLR higher than 2.73 (p = 0.0126), the platelet-to-lymphocyte ratio (PLR) higher than 103.89 (p = 0.0147) and the lymphocyte-to-monocyte ratio (LMR) lower than 4.2 (p = 0.0445). A multivariate analysis demonstrated that the surgical margin (p = 0.013) and NLR (p = 0.001) were significantly associated with DFS. Tumor size (p = 0.010) and NLR (p = 0.013) were independent prognostic factors for OS. CONCLUSIONS: This study had the second largest sample around the world and preoperative NLR may be a useful prognostic factor in CCS patients after radical surgery.

microRNA-124 inhibits bone metastasis of breast cancer by repressing Interleukin-11.

BACKGROUND: Most patients with breast cancer in advanced stages of the disease suffer from bone metastases which lead to fractures and nerve compression syndromes. microRNA dysregulation is an important event in the metastases of breast cancer to bone. microRNA-124 (miR-124) has been proved to inhibit cancer progression, whereas its effect on bone metastases of breast cancer has not been reported. Therefore, this study aimed to investigate the role and underlying mechanism of miR-124 in bone metastases of breast cancer. METHODS: In situ hybridization (ISH) was used to detect the expression of miR-124 in breast cancer tissues and bone metastatic tissues. Ventricle injection model was constructed to explore the effect of miR-124 on bone metastasis in vivo. The function of cancer cell derived miR-124 in the differentiation of osteoclast progenitor cells was verified in vitro. Dual-luciferase reporter assay was conducted to confirm Interleukin-11 (IL-11) as a miR-124 target. The involvement of miR-124/IL-11 in the prognosis of breast cancer patients with bone metastasis was determined by Kaplan-Meier analysis. RESULTS: Herein, we found that miR-124 was significantly reduced in metastatic bone tissues from breast cancers. Down-regulation of miR-124 was associated with aggressive clinical characteristics and shorter bone metastasis-free survival and overall survival. Restoration of miR-124 suppressed, while inhibition of miR-124 promoted the bone metastasis of breast cancer cells in vivo. At the cellular level, gain of function and loss-of function assays indicated that cancer cell-derived miR-124 inhibited the survival and differentiation of osteoclast progenitor cells. At the molecular level, we demonstrated that IL-11 partially mediated osteoclastogenesis suppression by miR-124 using in vitro and in vivo assays. Furthermore, IL-11 levels were inversely correlated with miR-124, and up-regulation IL-11 in bone metastases was associated with a poor prognosis. CONCLUSIONS: Thus, the identification of a dysregulated miR-124/IL-11 axis helps elucidate mechanisms of breast cancer metastases to bone, uncovers new prognostic markers, and facilitates the development of novel therapeutic targets to treat and even prevent bone metastases of breast cancer.

LncRNA MALAT1 Promotes Cancer Metastasis in Osteosarcoma via Activation of the PI3K-Akt Signaling Pathway.

BACKGROUND/AIMS: LncRNAs have been reported to be vital regulators of the progression of osteosarcoma, although the underlying mechanisms are not completely understood. METHODS: The levels of MALAT1 and miR-129-5p expression were measured using qRT-PCR. Cell growth was determined using the CCK-8 and colony formation assays. Cell migration and invasion were detected using the wound healing and Transwell invasion assays, respectively. Tumor growth was determined with a xenograft model. RESULTS: MALAT1 was significantly up-regulated in osteosarcoma tissues compared with adjacent non-tumor soft tissues. Overexpression of MALAT1 promoted osteosarcoma cell proliferation, migration, and invasion in vitro and enhanced tumor growth in a tumor xenograft mouse model. MALAT1 promoted osteosarcoma progression by modulating stem cell-like properties. Moreover, rescue experiment and luciferase reporter assay results indicated that MALAT1 modulates RET expression by sponging miR-129-5p in osteosarcomas. Furthermore, MALAT1 augmented the expression of downstream proteins of the RET-Akt pathway. MALAT1 was consistently significantly increased in osteosarcoma tissues and MALAT1 expression was positively correlated with tumor size and metastasis. High expression of MALAT1 was significantly associated with poor outcomes in patients with osteosarcomas. MALAT1 expression was positively related to RET and negatively related to miR-129-5p in osteosarcoma samples and xenograft tumors. MALAT1 functioned as an oncogenic lncRNA in osteosarcomas and was as an independent prognostic indicator. CONCLUSION: Our data revealed for the first time that MALAT1 increases stem cell-like properties by up-regulating RET via sponging miR-129-5p, and thus activates the PI3K-Akt signaling pathway and provides potential therapeutic targets for osteosarcoma treatment.

MFAP5 promotes tumor progression and bone metastasis by regulating ERK/MMP signaling pathways in breast cancer.

Breast cancer accounts for about 30% of all cancers in women, while approximately 70% breast cancer patients developed bone metastases throughout the course of their disease, highlighting the importance of exploring new therapeutic targets. Microfibrillar-associated protein 5 (MFAP5) is a component of extracellular elastic microfibril which has been confirmed to function in tissue development and cancer progression. But the role of MFAP5 in breast cancer remains unclear. The present study demonstrated that MFAP5 was up-regulated in breast cancers compared with that in normal breast tissues, and further increased in breast cancer bone metastasis. Functionally, MFAP5 overexpression accelerated breast cancer cell proliferation and migration, while an opposite effect was observed when MFAP5 was knocked down. In addition, up-regulation of MFAP5 increased the expression of MMP2 and MMP9 and activated the ERK signaling pathway. Conversely, inhibition of MFAP5 suppressed the expression of MMP2, MMP9, p-FAK, p-Erk1/2 and p-cJun. These findings may provide a better understanding about the mechanism of breast cancer and suggest that MFAP5 may be a potential prognostic biomarker and therapeutic target for breast cancer, especially for bone metastasis of breast cancer.

Treatment and outcome of metastatic paraganglioma of the spine.

BACKGROUND: Spinal metastatic paraganglioma (MPG) is rare and only reported in individual case reports. The low incidence makes it difficult to define appropriate therapy and prognosis. Our study illustrated the largest series to discuss the possible treatment and outcomes of patients with spinal MPG. METHODS: A retrospective study of 15 patients with spinal MPG who were surgically treated between 2005 and 2014 was performed. Three surgical modalities were applied, and radiotherapy and chemotherapy were utilized as adjuvant therapy. RESULTS: The mean patients age was 40.9 (range 23-58) years. The period between primary surgery and spinal metastasis averaged 8.2 (0.5-15) years. Lesions were mainly located in cervical spine (2), thoracic spine (8), lumbar spine (3), and sacrum (2). The mean follow-up period was 35.0 months. Lesion progression was detected in nine patients, whereas five patients (33.3%) passed away. For solitary spine, multiple bone and both bone and nonosseous metastasis cases, the mean progression-free survival was 41 (range 9-56), 22.5 (range 12-38) and 8.3 (range 3-18) months, respectively. CONCLUSIONS: The cases presented in the current study highlight the crucial role of surgery. Total en bloc for solitary spinal MPG could result in a satisfying prognosis and piecemeal total resection with postoperative radiotherapy could be an alternative therapy. Radiotherapy and chemotherapy were advocated, especially for the multiple metastasis.