Identification of ARAP3 as a regulator of tumor progression, macrophage infiltration and osteoclast differentiation in a tumor microenvironment-related prognostic model of Ewing sarcoma.

Understanding the specificity and complexity of the tumor microenvironment (TME) of Ewing sarcoma (ES) is essential for identifying the immune characteristics of ES, improving the prediction of immunotherapeutic response, and facilitating therapeutic target discovery. In this study, we not only evaluated the gene sets associated with TME in ES using ESTIMATE and WGCNA algorithms based on the transcriptome data of ES, but also constructed a prognostic model (ES Score) using univariate Cox regression and Lasso regression and assessed its predictive ability on immune cell infiltration. Subsequently, we identified ARAP3 as a key gene affecting the TME of ES. In addition, bioinformatic analyses and in vitro experiments proved that the high expression of ARAP3 regulated ES cell proliferation, migration, as well as apoptosis via the p53 signaling pathway and affected macrophage infiltration and osteoclast differentiation through regulating IL1B and IL11 secretion of tumor cells.

A novel molecular classification method for osteosarcoma based on tumor cell differentiation trajectories.

Subclassification of tumors based on molecular features may facilitate therapeutic choice and increase the response rate of cancer patients. However, the highly complex cell origin involved in osteosarcoma (OS) limits the utility of traditional bulk RNA sequencing for OS subclassification. Single-cell RNA sequencing (scRNA-seq) holds great promise for identifying cell heterogeneity. However, this technique has rarely been used in the study of tumor subclassification. By analyzing scRNA-seq data for six conventional OS and nine cancellous bone (CB) samples, we identified 29 clusters in OS and CB samples and discovered three differentiation trajectories from the cancer stem cell (CSC)-like subset, which allowed us to classify OS samples into three groups. The classification model was further examined using the TARGET dataset. Each subgroup of OS had different prognoses and possible drug sensitivities, and OS cells in the three differentiation branches showed distinct interactions with other clusters in the OS microenvironment. In addition, we verified the classification model through IHC staining in 138 OS samples, revealing a worse prognosis for Group B patients. Furthermore, we describe the novel transcriptional program of CSCs and highlight the activation of EZH2 in CSCs of OS. These findings provide a novel subclassification method based on scRNA-seq and shed new light on the molecular features of CSCs in OS and may serve as valuable references for precision treatment for and therapeutic development in OS.

DJ-1 promotes osteosarcoma progression through activating CDK4/RB/E2F1 signaling pathway.

Osteosarcoma (OS) is a primary malignant tumor of the bone characterized by poor prognosis due to chemotherapy resistance and high recurrence rates. DJ-1 (PARK7) is known as an oncogene and its abnormal expression is related to the poor prognosis of various types of malignant tumors. It was found in this study that upregulated expression of DJ-1 was closely correlated with the prognosis of OS patients by promoting the proliferation, migration and chemotherapy resistance of OS cells in vitro through regulating the activity of CDK4 but not through the oxidation mechanism or AKT pathway. The combination of DJ-1 and CDK4 promoted RB phosphorylation, leading to the dissociation of E2F1 into the nucleus to regulate the expression of cell cycle-related genes. The tumor xenograft mouse model demonstrated that DJ-1 knockout suppressed tumor growth in vivo. All these findings indicate that DJ-1 can affect the occurrence and progression of OS by regulating the CDK/RB/E2F1axis, suggesting a novel therapeutic opportunity for OS patients.

Surgical efficacy and survival prediction of patients with unspecified malignant bone tumors.

BACKGROUND: The surgical efficacy and prognostic outcomes of patients with unspecific malignant bone tumors (UMBTs) remain unclear. The study is to address: 1) What are the clinicopathological features and prognostic determinants for patients with UMBTs? 2) Can a nomogram be developed for clinicians to predict the short and long-term outcomes for individuals with UMBTs? 3) Does surgery improve outcomes for UMBT patients who received radiotherapy or chemotherapy after balancing the confounding bias? METHODS: 400 UMBT patients were filtrated from the Surveillance, Epidemiology, and End Results database to assess the clinicopathological features, treatments, and factors affecting prognosis. The optimal cutoff values of continuous variables were identified by the x-tile software. Kaplan-Meier method and multivariate Cox proportional hazard modeling were performed to evaluate the independent prognostic factors. Nomogram was further developed by using R software with rms package. The surgical efficacy was further assessed for patients receiving radiotherapy or chemotherapy after performing propensity score matching. RESULTS: The enrolled cohort included 195 (48.8%) female and 205 (51.2%) male patients. The 2- and 5-year cancer-specific survival (CSS) and overall survival (OS) rate were 58.2 ± 3.0%, 46.8 ± 3.2%, and 46.5 ± 2.6%, 34.4 ± 2.5%, respectively. Nomogram was finally developed for CSS and OS according to the identified independent factors: age, tumor extent, primary tumor surgery, tumor size, and pathology grade. For UMBT patients who received radiotherapy or chemotherapy, surgical intervention was associated with better CSS (pr = 0.003, pc = 0.002) and OS (pr = 0.035, pc = 0.002), respectively. CONCLUSIONS: Nomogram was developed for individual UMBT patient to predict short and long-term CSS and OS rate, and more external patient cohorts are warranted for validation. Surgery improves outcomes for UMBT patients who received either radiotherapy or chemotherapy.

Surgical management of de novo metastatic meningioma of the spine: An underestimated issue for WHO grade II/III meningiomas.

OBJECTIVES: Meningioma is a slow-growing neoplasm derived from meningothelial cells. Extradural metastasis of WHO grade II/III meningiomas is relatively rare, and spinal metastatic meningiomas (SMM) have only been described in individual case reports. The aim of the present study is to discuss the clinical features and treatments of SMM patients. METHODS: Fourteen SMM patients who received surgery in our center between 2010 and 2020 were reviewed retrospectively. Possible prognostic factors affecting local progression-free survival (LPFS) and overall survival (OS) were analyzed by log-rank analysis. RESULTS: Our series comprised nine men and five women, with a median age of 49 years. The interval from the primary treatment to SMM varied from 1 to 11 years. Lesions were mainly located in the lumbar-sacral region (7/14, 50.0%), followed by the thoracic spine (5/14, 35.7%) and cervical (2/14, 14.3%) spine. The median follow-up period was 42.7 months, during which six patients (42.9%) passed away. Local tumor progression was detected in four patients (28.6%). Log-rank analysis indicated that circumferential surgery was associated with good LPFS, whereas WHO grade III and visceral metastasis were factors adversely affecting OS. CONCLUSIONS: SMM is a challenging clinical entity, usually occurring in the fourth to fifth decades of life. Circumferential surgery is associated with good LPFS. WHO grade III and visceral metastasis are factors adversely affecting OS of patients with SMM. Long-term follow-up is recommended for patients who have received surgical treatment for primary meningiomas (Simpson Grade III/IV), especially for WHO III lesions.

Identifying the Risk Factors and Estimating the Prognosis in Patients with Pelvis and Spine Ewing Sarcoma: A Population-Based Study.

STUDY DESIGN: Retrospective analysis. OBJECTIVE: The study was designed to: (1) figure out risk factors of metastasis; (2) explore prognostic factors and develop a nomogram for pelvis and spine Ewing sarcoma (PSES). SUMMARY OF BACKGROUND DATA: Tools to predict survival of PSES are still insufficient. Nomogram has been widely developed in clinical oncology. Moreover, risk factors of PSES metastasis are still unclear. METHODS: The data were collected and analyzed from the Surveillance, Epidemiology, and End Results (SEER) database. The optimal cutoff values of continuous variables were identified by X-tile software. The prognostic factors of survival were performed by Kaplan-Meier method and multivariate Cox proportional hazards modeling. Nomograms were further constructed for estimating 3- and 5-year cancer-specific survival (CSS) and overall survival (OS) by using R with rms package. Meanwhile, Pearson χ2 test or Fisher exact test, and logistic regression analysis were used to analyze the risk factors for the metastasis of PSES. RESULTS: A total of 371 patients were included in this study. The 3- and 5-year CSS and OS rate were 65.8 ±â€Š2.6%, 55.2 ±â€Š2.9% and 64.3 ±â€Š2.6%, 54.1 ±â€Š2.8%, respectively. The year of diagnosis, tumor size, and lymph node invasion were associated with metastasis of patients with PSES. A nomogram was developed based on identified factors including: age, tumor extent, tumor size, and primary site surgery. The concordance index (C-index) of CSS and OS were 0.680 and 0.679, respectively. The calibration plot showed the similar trend of 3-year, 5-year CSS, and OS of PSES patients between nomogram-based prediction and actual observation, respectively. CONCLUSION: PSES patients with earlier diagnostic year (before 2010), larger tumor size (>59 mm), and lymph node invasion, are more likely to have metastasis. We developed a nomogram based on age, tumor extent, tumor size, and surgical treatments for determining the prognosis for patients with PSES, while more external patient cohorts are warranted for validation.Level of Evidence: 3.

Targeting nanoparticles for diagnosis and therapy of bone tumors: Opportunities and challenges.

A variety of targeted nanoparticles were developed for the diagnosis and therapy of orthotopic and metastatic bone tumors during the past decade. This critical review will focus on principles and methods in the design of these bone-targeted nanoparticles. Ligands including bisphosphonates, aspartic acid-rich peptides and synthetic polymers were grafted on nanoparticles such as PLGA nanoparticles, liposomes, dendrimers and inorganic nanoparticles for bone targeting. Besides, other ligands such as monoclonal antibodies, peptides and aptamers targeting biomarkers on tumor/bone cells were identified for targeted diagnosis and therapy. Examples of targeted nanoparticles for the early detection of bone metastatic tumors and the ablation of cancer via chemotherapy, photothermal therapy, gene therapy and combination therapy will be intensively reviewed. The development of multifunctional nanoparticles to break down the "vicious" cycle between tumor cell proliferation and bone resorption, and the challenges and perspectives in this area will be discussed.

Prognostic Significance of a Novel Score Model Based on Preoperative Indicators in Patients with Breast Cancer Spine Metastases (BCSM).

BACKGROUND: Surgery remains the mainstay of treatment for breast cancer spinal metastasis (BCSM) to relieve symptoms and improve the quality of life of BCSM patients. Therefore, it is important to effectively predict the prognosis of patients to determine whether they can undergo surgical operation. However, the prevalent methods for prognosis evaluation lack specificity and sensitivity for indicated malignancies like breast cancer because they are built on a relatively small number of heterogeneous types of primary tumors. The aim of the present study was to explore a novel predictive model based on the clinical, pathological and blood parameters obtained from BCSM patients before they received surgical intervention. METHODS: Altogether, 144 patients were included in this study. Univariate and multivariate analyses were performed to investigate the significance of preoperative parameters and identify independent factors for prognostic prediction of BCSM. A nomogram for survival prediction was then established and validated. Time-dependent ROC (TDROC) curves were graphed to evaluate the accuracy of the novel model vs other scoring systems including Tomita Score, revised Tokuhashi Score, modified Bauer Score and New England Spinal Metastasis Score. P values <0.05 were considered statistically significant. RESULTS: Independent factors, including preoperative postmenopausal (P=0.034), visceral metastasIs (P=0.021), preoperative Frankel Score (P=0.001), estrogen receptor status (P=0.014), platelet-to-lymphocyte ratio (P=0.012), lymphocyte-monocyte ratio (P<0.001) and albumin-globulin ratio (P=0.017), were selected into the nomogram model with the C-index of 0.834 (95% CI, 0.789-0.890). TDROC curves showed that the Changzheng Hospital (CZ) Score system had the best performance and exhibited the largest IAUC value in comparison with the other scoring systems. CONCLUSION: We constructed a nomogram model known as CZ Score based on the significant factors to predict the prognosis for BCSM patients. The result showed that CZ Score had a better value for prognostic evaluation and surgical decision-making as compared with the other scoring systems.

Carrier-Free Platinum Nanomedicine for Targeted Cancer Therapy.

Numerous nanomedicines have been developed to improve the efficiency and safety of conventional anticancer drugs; however, the complexities in carrier materials and functional integration make it challenging to promote these candidates for clinical translation. In this study, a facile method to prepare carrier-free anticancer nanodrug with inherent bone targeting and osteoclastogenesis inhibition capabilities is reported. Phytic acid, a naturally occurring and nontoxic product, is reacted with cisplatin to form uniform nanoparticles of different sizes. The prepared nanoparticles possess high drug loading and pH-responsive drug release behaviors. Phytic acid in the nanomedicine ensures high bone targeting and osteoclastogenesis inhibition, and the released platinum drugs triggered by tumor extracellular acidity eradicate tumor cells. The nanomedicine around 100 nm shows high anticancer activity and much reduced side effects in a subcutaneous breast cancer model when compared with cisplatin. In addition, it shows high accumulation at osteolytic lesions, and efficiently inhibits tumor growth and tumor-associated osteolysis in a bone metastatic breast cancer model. Here, a facile and efficient strategy to prepare carrier-free nanomedicines with high anticancer drug loading, inherent bone targeting, and osteoclast inhibitory activities for cancer therapy is provided.

NAT1 promotes osteolytic metastasis in luminal breast cancer by regulating the bone metastatic niche via NF-κB/IL-1B signaling pathway.

Breast cancer is a molecularly heterogeneous disease that can be subdivided into different subtypes. Compared with the other subtypes, luminal breast cancer (LBC) is considered more susceptible to bone metastasis. However, the intrinsic mechanisms remain elusive. Bioinformatics analysis of the preset study showed that N-acetyltransferase 1 (NAT1) was specifically expressed in LBC and closely correlated with bone metastasis. In addition, NAT1 could promote LBC cell migration and clonal formation, induce osteoclast differentiation and raise the Rankl/Opg ratio in osteoblasts. Our in vivo experiment demonstrated that NAT1 promoted LBC bone metastasis and bone destruction, which could be reversed by NAT1 inhibitor treatment. The result of cytokine array showed that NAT1 could significantly over activate the NF-κB signaling pathway and up-regulate the expression of IL-1B, which further worked as downstream factors in these processes. All these results demonstrated NAT1 was up-regulated in LBC and promoted the formation of bone metastatic niche and osteolytic bone metastasis through the NAT1/NF-κB/IL-1B axis. This finding may provide a new pathway to help understand the mechanisms of LBC bone metastasis and suggest a novel therapeutic and diagnostic target for its treatment.

Treatment strategies and outcomes for spinal rhabdomyosarcoma: A series of 11 cases in a single center and review of the literature.

OBJECTIVES: Rhabdomyosarcoma (RMS) involving the spine is rare. The aim of the present study is to explore the clinicopathological features, surgical treatments and outcomes of this rare disease. PATIENTS AND METHODS: Eleven patients with spinal RMS who received surgery in our institution between 2012 and 2018 were retrospectively investigated. The literature on spinal RMS was also reviewed. RESULTS: Our study consisted of 7 cases of primary RMS and 4 cases of metastatic RMS. Seven primary and one metastatic spinal RMS received radical resection, the remaining three metastatic patients received palliative resection. Eight patients died with a median survival time of 8 months. The mean value of Ki-67 positivity was 48.2 %. Literature review revealed a total of 22 previously reported cases. 54.5 % of the pooled cases of the 33 patients were under the age of 18. Of the 20 patients with primary spinal RMS, 9 cases were diagnosed as embryonal, while 6 of the 13 metastatic patients were diagnosed as alveolar. Multiple modalities, including surgery and concurrent adjuvant therapy were performed in 19 patients. The median overall survival (OS) for 28 patients with detailed follow-up information was 10 months. Radical resection offered a significant longer median OS than non-radical resection (18 vs. 6 months, p = 0.027). CONCLUSION: Spinal RMS mainly affects young patients. The embryonal form and alveolar form is the most frequent subtype for primary and metastatic spinal RMS respectively. Spinal RMS is highly aggressive with dismal prognosis. Multimodality therapies are the mainstay of treatment. Radical resection is strongly recommended in eligible patients.

Secondary aneurysmal bone cyst of the spine: Clinicopathological features, surgical modalities and outcomes.

OBJECTIVES: Spinal secondary aneurysmal bone cyst (SABC) is extremely rare with few published reports available at present. Our aim is to explore the clinicopathologic features, surgical modalities and outcomes of spinal SABC. PATIENTS AND METHODS: A retrospective study of 33 patients with spinal SABC who were surgically treated in our center between 2010 and 2018 was performed. Clinical data, treatment options, complications and outcomes were analyzed. RESULTS: Of the 33 patients, 12 were male and 21 were female, with a mean age of 32 years. Eleven lesions were located at the lumbar spine. The underlying lesions included giant cell tumor (GCT) (n = 20), osteoblastoma (n = 7), hemangiaoma (n = 3), fibrous dysplasia (n = 2) and osteosarcoma (n = 1). Preoperative selective arterial embolization was applied in 24 patients. All the patients were treated surgically through either subtotal resection (n = 1), piecemeal total resection (n = 21), or total en bloc resection (n = 11). Four patients experienced recurrence and one patient died during the follow-up period. CONCLUSION: Spinal SABC is popular in the third and fourth decade of life with female predominance. GCT is the most common underlying lesion. Preoperative arterial embolization is recommended, while surgery is the mainstay of treatment for spinal SABC. En bloc resection is recommended for spinal SABCs especially when underlying tumor is aggressive or malignant.

Recurrence or neurological loss? Resection mode selection for patients with large sacral chordoma: an analysis of prognostic factors and quality of life.

BACKGROUND: Surgical resection represents the main therapeutic method for sacral chordoma, but plans for resection mode must weigh neurological loss against complete tumor excision, a difficult balance to strike. The purpose of this study was to provide useful information contributing to surgical decision making in sacral chordoma. METHODS: A retrospective review was performed on 47 patients with large sacral chordoma. Prognostic factors affecting recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox proportional hazards model. Quality of life was assessed by the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire and compared using Student's t test. RESULTS: Resection mode was the independent prognostic factor affecting RFS, while independent prognostic factors affecting OS were resection mode and postoperative recurrence. As for quality of life, the en bloc resection group showed a higher score in emotional well-being, while the piecemeal resection group scored better in function well-being. No significant difference was identified in total the FACT-G score between two groups. CONCLUSIONS: On the one hand, en bloc resection showed huge advantages in disease control for sacral chordoma. On the other hand, despite the unsatisfaction in functional well-being, en bloc resection did not sacrifice quality of life significantly in terms of the total FACT-G score.

Symptomatic aneurysmal bone cysts of the spine: clinical features, surgical outcomes, and prognostic factors.

PURPOSE: The aim of the study was to report the long-term outcomes and analyze the potential prognostic factors that may contribute to symptomatic patients with aneurysmal bone cyst (ABC) of the spine undergoing surgical treatments. METHODS: A retrospective analysis of consecutive patients with ABCs of the spine was performed. The clinical features were reviewed, and the disease-free survival (DFS) and overall survival (OS) rates were estimated using the Kaplan-Meier method. Factors with p values ≤ 0.05 were subjected to multivariate analysis by Cox proportional hazards model to identify the independent prognostic contributors. p values < 0.05 were considered statistically significant. RESULTS: A total of 42 patients with ABCs of the spine were included in the study. All patients received surgical treatments. The mean follow-up period was 41.3 months (median 39.5, range 24-64). Local recurrence was detected in eight patients after surgery in our center, whereas death occurred in three patients. The estimated 5-year DFS and OS rate was 54.1% and 76.8%, respectively. The statistical analyses indicated that both en bloc resection and primary/secondary tumor status were independent prognostic factors for DFS. CONCLUSIONS: Secondary ABC status may be associated with worse prognosis, and en bloc resection remains the treatment of choice for ABCs with neurologic deficits or spinal instability of the spine, which is correlated with better prognosis for local tumor control. These slides can be retrieved under Electronic Supplementary Material.

FOXD3 Suppresses Tumor-Initiating Features in Lung Cancer via Transcriptional Repression of WDR5.

The tumor-initiating cells (TICs) are a cell population that can initiate tumor occurrence, mediate drug resistance, and give rise to metastasis. FOXD3 is a forkhead box (Fox) transcription factor family that regulates the pluripotency of embryonic stem cell and tumorigenicity. However, it is unclear whether FOXD3 plays any role in TIC and tumor metastasis. The functional analysis of FOXD3 was performed by oncospheres formation and redifferentiation, drug resistance assay, and cell migration. Global genomic RNA-Seq and ChIP-Seq analysis were used to identify the direct target of FOXD3 in lung cancer. We demonstrated that downregulation of FOXD3 in TICs was positively correlated with higher histologic grades and positive lymph node metastasis. FOXD3 repressed TIC expansion and cell migration, drug resistance, and osteoclasts in vitro and in vivo. Mechanically, we found that FOXD3 represses WDR5, which regulates TIC-related signaling pathway. Moreover, WDR5 were positively correlated with the TIC abundance and tumor progression. Besides, patients with high expression of WDR5 presented a poorer overall survival. FOXD3 may suppress TIC accumulation by repressing the expression of WDR5 in lung cancer. Stem Cells 2019;37:582-592.

A pH-responsive hydrogel with potent antibacterial activity against both aerobic and anaerobic pathogens.

Aminoglycosides are a family of antibiotics with a wide-spread antibacterial spectrum and high antibacterial activity. However, they are less effective against anaerobic pathogens due to the requirement of aerobic respiration to exert their antibacterial functions. Here, we prepared a pH-responsive hydrogel with potent antibacterial activities against both aerobic and anaerobic pathogens. The hydrogel was prepared by reacting oxidized dextran with aminoglycoside and an ornidazole analogue via an acid-labile Schiff base linkage. The prepared hydrogel was injectable, self-healing, biocompatible, and showed a pH-responsive drug release behavior. More importantly, the gel was efficient in killing both aerobic and anaerobic pathogens. This study provides a facile strategy to expand the antibacterial spectrum of aminoglycoside hydrogels.

One stone with two birds: Phytic acid-capped platinum nanoparticles for targeted combination therapy of bone tumors.

Targeted drug delivery to malignant bone lesions remains a challenging task in the treatment of bone tumors. In this article, we reported a naturally occurring phytic acid (PA) with both bone-targeting capability and anticancer activity. The PA-capped platinum nanoparticles showed high affinity to hydroxyapatite in vitro and in vivo, and maintained both the inherent anticancer ability of PA and photothermal effect of platinum nanoparticles. PA-capped nanoparticles displayed a 4-fold higher accumulation in the osteolytic lesions than sodium citrate-templated ones, and efficiently inhibited bone tumor growth and the tumor associated-osteolysis upon exposure to a near-infrared light. This study provides a novel and efficient strategy to prepare bone-targeted nanoparticles with inherent anticancer activity for combination therapy of malignant bone tumors.

A Targeted and pH-Responsive Bortezomib Nanomedicine in the Treatment of Metastatic Bone Tumors.

Bortezomib is a boronate proteasome inhibitor widely used as an efficient anticancer drug; however, the clinical use of bortezomib is hampered by its adverse effects such as hematotoxicity and peripheral neuropathy, and low efficacy on solid tumors due to unfavorable pharmacokinetics and poor penetration in the solid tumors. In this study, we developed a tripeptide Arg-Gly-Asp (RGD)-targeted dendrimer conjugated with catechol and poly(ethylene glycol) groups for the targeted delivery of bortezomib to metastatic bone tumors. Bortezomib was loaded on the dendrimer via a boronate-catechol linkage with pH-responsive property, which plays an essential role in the control of bortezomib loading and release. The nontargeted bortezomib nanomedicine showed minimal cytotoxicity at pH 7.4, but significantly increased anticancer activity when cyclic RGD (cRGD) moieties were anchored on the dendrimer surface. The ligand cRGD enabled efficient internalization of the bortezomib complex by breast cancer cells such as MDA-MB-231 cells. The targeted nanomedicine efficiently depressed the progression of metastatic bone tumors and significantly inhibited the tumor-associated osteolysis in a model of bone tumors. This study provided an insight into the development of nanomedicine for metastatic bone tumors.

Multifunctional melanin-like nanoparticles for bone-targeted chemo-photothermal therapy of malignant bone tumors and osteolysis.

Malignant bone tumors associated with aggressive osteolysis are currently hard to be cured by the clinical strategies. Nevertheless, nanomedicine might provide a promising therapeutic opportunity. Here, we developed a multifunctional melanin-like nanoparticle for bone-targeted chemo-photothermal treatment of malignant bone tumors. The particle was originally fabricated from alendronate-conjugated polydopamine nanoparticle (PDA-ALN) that exhibited excellent photothermal effect and high affinity to hydroxyapatite. PDA/Fe-ALN significantly enhanced the magnetic resonance contrast of the bone tumors in vivo, suggesting that more PDA-ALN accumulated at the osteolytic bone lesions in the tumors compared with the non-targeting PDA. Chemodrug SN38 was efficiently loaded on PDA-ALN, and the drug release could be triggered by near-infrared irradiation and acidic stimulus. Finally, the combined chemo-photothermal therapy efficiently suppressed the growth of bone tumors and reduced the osteolytic damage of bones at a mild temperature around 43 °C. This study provides an efficient and robust nanotherapeutics for the treatment of malignant bone tumors.

miR-215 suppresses proliferation and migration of non-small cell lung cancer cells.

The expression of microRNA-215 (miR-215) in non-small cell lung cancer (NSCLC) tissues and the effects of miR-215 on the proliferation and migration of NSCLC cells were investigated. qRT-PCR was used to detect the expression of miR-215 in NSCLC tissues and paired normal tumor-adjacent lung tissues; MTT assay, transwell assay and soft-agar assay were used in vitro to evaluate the role of miR-215 on proliferation, migration and cell clonality on NSCLC cells, after transfecting miR-215 mimics to NSCLC cell line A549 or miR-215 to H1299. miR-215 was significantly decreased in NSCLC tissues compared to the paired normal tissues; Overexpression of miR-215 in A549 cells resulted in reduction of the cell proliferation, migration and cell clonality, while downregulation of miR-215 in H1299 cells could promote cell proliferation, migration and clonality. In conclusion, miR-215 was downregulated in NSCLC tissues and may play a key role in the development of NSCLC.