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.

Soft-tissue reconstruction with pedicled vertical rectus abdominis myocutaneous flap after total or high sacrectomy for giant sacral tumor.

BACKGROUND: The large soft-tissue defect after total or high sacrectomy for giant sacral tumor induces high incidence of wound complications. It remains a huge challenge to reconstruct the soft-tissue defect and achieve the preferred clinical outcome. METHODS: A total of 27 patients undergoing one-stage total or high sacrectomy for giant sacral tumors between 2016 and 2021 in a tertiary university hospital were retrospectively reviewed. Participants were divided into two groups. Thirteen patients underwent a pedicled vertical rectus abdominis myocutaneous (VRAM) flap reconstruction, whereas 14 patients underwent a conventional wound closure. Patient's clinical characteristics, surgical duration, postoperative complications, and outcomes were compared between the two groups. RESULTS: Patients in VRAM and non-VRAM groups were similar in baseline characteristics. The mean tumor size was 12.85 cm (range: 10-17 cm) in VRAM group and 11.79 cm (range: 10-14.5 cm) in non-VRAM group (P = 0.139). The most common giant sacral tumor is chordoma. Patients in VRAM group had a shorter length of drainage (9.85 vs 17.14 days), postoperative time in bed (5.54 vs 17.14 days), and total length of stay (19.46 vs 33.36 days) compared with patients in non-VRAM group. Patients in the VRAM group had less wound infection and debridement than patients in non-VRAM group (15.4% vs 57.1%, P < 0.001). CONCLUSIONS: This study demonstrates the advantages of pedicled VRAM flap reconstruction of large soft-tissue defects after high or total sacrectomy using the anterior-posterior approach. This choice of reconstruction is better than direct wound closure in terms of wound infection, length of drainage, and total length of stay.

Single-cell profiling of the microenvironment in human bone metastatic renal cell carcinoma.

Bone metastasis is of common occurrence in renal cell carcinoma with poor prognosis, but no optimal treatment approach has been established for bone metastatic renal cell carcinoma. To explore the potential therapeutic targets for bone metastatic renal cell carcinoma, we profile single cell transcriptomes of 6 primary renal cell carcinoma and 9 bone metastatic renal cell carcinoma. We also include scRNA-seq data of early-stage renal cell carcinoma, late-stage renal cell carcinoma, normal kidneys and healthy bone marrow samples in the study to better understand the bone metastasis niche. The molecular properties and dynamic changes of major cell lineages in bone metastatic environment of renal cell carcinoma are characterized. Bone metastatic renal cell carcinoma is associated with multifaceted immune deficiency together with cancer-associated fibroblasts, specifically appearance of macrophages exhibiting malignant and pro-angiogenic features. We also reveal the dominance of immune inhibitory T cells in the bone metastatic renal cell carcinoma which can be partially restored by the treatment. Trajectory analysis showes that myeloid-derived suppressor cells are progenitors of macrophages in the bone metastatic renal cell carcinoma while monocytes are their progenitors in primary tumors and healthy bone marrows. Additionally, the infiltration of immune inhibitory CD47+ T cells is observed in bone metastatic tumors, which may be a result of reduced phagocytosis by SIRPA-expressing macrophages in the bone microenvironment. Together, our results provide a systematic view of various cell types in bone metastatic renal cell carcinoma and suggest avenues for therapeutic solutions.

Prediction and related genes of cancer distant metastasis based on deep learning.

Cancer metastasis is one of the main causes of cancer progression and difficulty in treatment. Genes play a key role in the process of cancer metastasis, as they can influence tumor cell invasiveness, migration ability and fitness. At the same time, there is heterogeneity in the organs of cancer metastasis. Breast cancer, prostate cancer, etc. tend to metastasize in the bone. Previous studies have pointed out that the occurrence of metastasis is closely related to which tissue is transferred to and genes. In this paper, we identified genes associated with cancer metastasis to different tissues based on LASSO and Pearson correlation coefficients. In total, we identified 45 genes associated with bone metastases, 89 genes associated with lung metastases, and 86 genes associated with liver metastases. Through the expression of these genes, we propose a CNN-based model to predict the occurrence of metastasis. We call this method MDCNN, which introduces a modulation mechanism that allows the weights of convolution kernels to be adjusted at different positions and feature maps, thereby adaptively changing the convolution operation at different positions. Experiments have proved that MDCNN has achieved satisfactory prediction accuracy in bone metastasis, lung metastasis and liver metastasis, and is better than other 4 methods of the same kind. We performed enrichment analysis and immune infiltration analysis on bone metastasis-related genes, and found multiple pathways and GO terms related to bone metastasis, and found that the abundance of macrophages and monocytes was the highest in patients with bone metastasis.

Implant failure and revision strategies after total spondylectomy for spinal tumors.

Background: Although there have been several risk factors reported for implant failure (IF), little consensus exists. Potential applicable measures to protect patients from IF are relatively few. This study aimed to discover new risk factors for IF and explore potential protective measures from IF after total spondylectomy for spinal tumors. Methods: A total of 145 patients undergoing total spondylectomy for thoracic and lumbar spinal tumors between 2010 and 2021 were included from three tertiary university hospitals. Patient demographic and surgical characteristics and follow-up outcomes were collected. Results: During a mean follow-up of 53.77 months (range, 12 to 149 months), 22 of 145 patients (15.17%) developed IF. Patients undergoing thoracolumbar junctional region (T12/L1) resection were more likely to develop IF compared to those undergoing surgery at other vertebral levels (HR = 21.622, 95% CI = 3.567-131.084, P = 0.001). Patients undergoing titanium mesh cage reconstruction were more likely to develop IF compared to patients undergoing expandable titanium cage reconstruction (HR = 8.315, 95% CI = 1.482-46.645, P = 0.016). Patients with bone cement augmentation around the cage were less likely to develop IF compared to those not receiving bone cement augmentation (HR = 0.015, 95% CI = 0.002-0.107, P < 0.001). Of the 22 patients with IF, 14 (63.63%) accepted personalized revision surgery. Conclusion: The use of an expandable cage and the use of bone cement augmentation around the anterior column support cage are protective measures against IF after total spondylectomy.

Emulsion-oriented assembly for Janus double-spherical mesoporous nanoparticles as biological logic gates.

The ability of Janus nanoparticles to establish biological logic systems has been widely exploited, yet conventional non/uni-porous Janus nanoparticles are unable to fully mimic biological communications. Here we demonstrate an emulsion-oriented assembly approach for the fabrication of highly uniform Janus double-spherical MSN&mPDA (MSN, mesoporous silica nanoparticle; mPDA, mesoporous polydopamine) nanoparticles. The delicate Janus nanoparticle possesses a spherical MSN with a diameter of ~150 nm and an mPDA hemisphere with a diameter of ~120 nm. In addition, the mesopore size in the MSN compartment is tunable from ~3 to ~25 nm, while those in the mPDA compartments range from ~5 to ~50 nm. Due to the different chemical properties and mesopore sizes in the two compartments, we achieve selective loading of guests in different compartments, and successfully establish single-particle-level biological logic gates. The dual-mesoporous structure enables consecutive valve-opening and matter-releasing reactions within one single nanoparticle, facilitating the design of single-particle-level logic systems.

Modified Iliac Screw in Lumbopelvic Fixation After Sacral Tumor Resection: A Single-Center Case Series.

BACKGROUND: Traditional iliac screw, S2-alar iliac screw, and modified iliac screw are the 3 common techniques for lumbopelvic fixation. The application of the modified iliac technique in sacral spinal tumors has been rarely reported. OBJECTIVE: To report the feasibility and safety of modified iliac screws after sacral tumor resection and their preliminary clinical outcomes. METHODS: Twenty-seven patients who underwent sacral tumor resection with modified iliac screw fixation between August 2017 and August 2021 at our center were clinically and radiographically evaluated. RESULTS: A total of 59 iliac screws were inserted by freehand according to the anatomic landmarks. The mean operation time was 207 minutes (range, 140-435 minutes). The average estimated blood loss was 1396 mL (300-4200 mL). Computed tomography scans showed that 2 (3.4%) screws penetrated the iliac cortex, indicating a 96.6% implantation accuracy rate. There were no iatrogenic neurovascular or visceral structure complications observed. The mean minimal distances from the screw head to the skin were 24.9 and 25.8 mm on the left and right sides, respectively. The mean minimal distances from the screw head to the horizontal level of the posterior superior iliac spine were 7.9 and 8.3 mm on the left and right sides, respectively. Two patients (7.4%) underwent reoperation for wound infection. At the latest follow-up, no patient had complications of screw head prominence, pseudarthrosis, or instrument failure. CONCLUSION: The modified iliac screw is characterized by its minimal invasiveness and simplicity of placement. It is an ideal alternative for lumbopelvic fixation after sacral tumor resection.

3D-Printed Patient-Customized Artificial Vertebral Body for Spinal Reconstruction after Total En Bloc Spondylectomy of Complex Multi-Level Spinal Tumors.

Three dimensional (3D)-printing technology facilitates complex spine surgery with unique advantages in artificial vertebral body design and manufacturing. In this study, we aimed to demonstrate how a 3D-printed spinal implant is utilized in the management of multi-level spinal tumors and integrates with comprehensive oncologic treatment. Eight spinal or paraspinal tumor patients requiring spinal reconstruction after total en bloc spondylectomy were selected as candidates for 3D-printed titanium artificial vertebral body implants. All patients underwent surgery on three or more vertebral segments or complex spinal junction segments. The clinical, oncological, and surgical characteristics of patients were collected. Of the eight candidates, seven suffered from pain and/or limb disorder. Six underwent successful 3D-printed spinal implantation, while two failed due to implant mismatching and were converted to conventional reconstruction. Of the six patients undergoing 3D-printed spinal implant surgery: (i) Five had recurrent tumors; (ii) three underwent neoadjuvant therapy; (iii) the median surgery time was 414 min; (iv) the median blood loss was 2150 ml; (v) the median blood transfusion was 2000 ml; (vi) the median length of hospital stay was 9 days; (vii) four patients received adjuvant therapy after surgery; and (viii) all patients experienced no pain, moved freely, and had no local recurrence at a median of 11.5 months post-operative follow-up. Spinal reconstruction with a 3D-printed titanium artificial vertebral body allows for total en bloc resection of complex multi-level spinal tumors. Combined with neoadjuvant and adjuvant therapy, these patients had excellent postoperative outcomes, long-term normal spinal function, and associated low local recurrence probability.

Freehand S2-Alar-Iliac Screw Placement Technique in Lumbosacral Spinal Tumors: A Preliminary Study.

OBJECTIVE: S2-alar-iliac (S2AI) screw technique is widely used in spinal surgery, but it is rarely seen in the field of spinal tumors. The aim of the study is to report the preliminary outcomes of the freehand S2AI screw fixation after lumbosaral tumor resection. METHODS: The records of patients with lumbosacral tumor who underwent S2AI screw fixation between November 2016 to November 2020 at our center were reviewed retrospectively. Outcome measures included operative time, blood loss, complications, accuracy of screws, screw breach, and overall survival. Mean ± standard deviation or range was used to present continuous variables. Kaplan-Meier curve was used to present postoperative survival. RESULTS: A total of 23 patients were identified in this study, including 12 males and 11 females, with an average age of 47.3 ± 14.5 (range,15-73). The mean operation time was 224.6 ± 54.1 (range, 155-370 min). The average estimated blood loss was 1560.9 ± 887.0 (600-4000 ml). A total of 46 S2AI screws were implanted by freehand technique. CT scans showed three (6.5%) screws had penetrated the iliac cortex, indicating 93.5% implantation accuracy rate. No complications of iatrogenic neurovascular or visceral structure were observed. The average follow-up time was 31.6 ± 15.3 months (range, 13-60 months). Two patients' postoperative plain radiography showed lucent zone around the screw. One patient underwent reoperation for wound delayed infection. At the latest follow-up, eight patients had tumor-free survival, 11 had survival with tumor, and four died of disease. CONCLUSION: The freehand S2AI screw technique is reproducible, safe, and reliable in the management of lumbosacral spinal tumors.

Computer-Aided Design and 3D Printing of Hemipelvic Endoprosthesis for Personalized Limb-Salvage Reconstruction after Periacetabular Tumor Resection.

3D-printed hemipelvic endoprosthesis is an emerging solution for personalized limb-salvage reconstruction after periacetabular tumor resection. Further clinical studies are still required to report its surgical characteristics, outcomes, benefits and drawbacks. Sixteen consecutive patients underwent periacetabular tumor wide resection and pelvic reconstruction with a 3D-printed hemipelvic endoprosthesis from 2018 to 2021. The surgical characteristics and outcomes are described. The mean follow-up duration was 17.75 months (range, 6 to 46 months). Five patients underwent surgery for type I + II resection and reconstruction, seven for type II + III resection and reconstruction, three for type II resection and reconstruction, and one for type I + II + IV resection and reconstruction. The incidence of postoperative complication was 12.5% (2/16) for deep venous thrombosis (DVT), 12.5% (2/16) for pneumonia, and 12.5% (2/16) for would deep or superficial infection. During follow-up, two patients (12.5%) suffered hip dislocation and underwent revision surgery. CT demonstrated an obvious prosthetic porous structure-bone fusion after follow-up of at least 6 months. At the final follow-up, 12 lived with no evidence of disease while four lived with disease; no patients experienced pain; and 15 had independent ambulation, with a mean Musculoskeletal Tumor Society (MSTS) score of 85.8% (range, 26.7% to 100%). 3D-printed hemipelvic endoprosthesis facilitates wide resection of periacetabular tumor and limb-salvage reconstruction, thus resulting in good oncological and functional outcomes. The custom-made nature is able to well mimic the skeletal anatomy and microstructure and promote osseointegration. Perioperative complications and rehabilitation exercise still need to be stressed for this engineering technology-assisted major orthopedic surgery.

Comparison of Surgical Outcomes Between Separation Surgery and Piecemeal Spondylectomy for Spinal Metastasis: A Retrospective Analysis.

Objective: This study aimed to compare the outcomes between piecemeal spondylectomy and separation surgery for patients with spinal metastasis. Summary of Background Data: Piecemeal spondylectomy and separation surgery are two widely-used treatment options for spinal metastasis. However, no studies have compared the surgical outcomes between both treatment modalities. Methods: Patients with spinal metastasis who underwent piecemeal spondylectomy or separation surgery between August 2017 and April 2020 at our spine center were recruited. Demographic, preoperative, perioperative, and follow-up data were collected and analyzed. Kaplan-Meier analysis and the log-rank test were used to analyze overall survival (OS) and progression-free survival (PFS) in patients with spinal metastasis. Results: Overall, 26 patients were treated with piecemeal spondylectomy, and 29 underwent separation surgery with postoperative stereotactic radiosurgery. Both groups showed significant postoperative improvements in neurological status. The piecemeal spondylectomy group had significantly more blood loss (1784.62 ± 833.64 vs. 1165.52 ± 307.38 ml) and required longer operative time (4.76 ± 0.93 vs. 3.73 ± 1.15 h) than the separation surgery group. No significant difference in OS was found between the groups (P = 0.064); however, patients in the separation surgery group experienced less local recurrence than those in the piecemeal spondylectomy group (P = 0.0014). Notably, significant differences were detected in the development of complications between the groups (P = 0.029). Conclusion: Separation surgery led to less blood loss and reduced complications and had shorter operation time than piecemeal spondylectomy. Although no significant differences were found in OS between the groups, separation surgery was associated with better PFS compared with piecemeal spondylectomy. These findings suggest that separation surgery has some advantages over piecemeal spondylectomy for patients with spinal metastatic disease.

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.

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.

Monodisperse Hollow MnO2 with Biodegradability for Efficient Targeted Drug Delivery.

The development of new nanocarriers with desired degradability and targeted ability is of great significance for efficient drug delivery. In this work, a monodisperse hollow structured MnO2 (H-MnO2) with a mesoporous shell is prepared and functionalized for efficient targeted drug delivery. The highly monodisperse H-MnO2 with a uniform morphology was obtained by in situ growing MnO2 on solid silica nanoparticles and subsequently removing the silica core. Then, the H-MnO2 is successively modified with polyethylene glycol and targeted molecule folate (FA). The resultant H-MnO2-FA shows excellent colloidal stability and high drug-loading content (∼58.2%) of the antitumor drug doxorubicin hydrochloride (DOX). The H-MnO2-FA possesses acid-responsive T1-weighted magnetic resonance imaging ability. The pH-dependent biodegradation behavior of H-MnO2-FA is directly observed in vitro and confirmed by in vivo imaging, which is expected to favor the potential clearance of this hollow structured nanocarrier and eliminate its long-term toxicity. In addition, the DOX-loaded H-MnO2-FA also demonstrates excellent cancer cell-killing effect and tumor inhibition efficacy.

Growth hormone receptor promotes osteosarcoma cell growth and metastases.

Osteosarcoma (OS) is the primary bone malignancy in children and adolescents, with a high incidence of lung metastasis and poor prognosis. Here, we report that growth hormone receptor (GHR) is overexpressed in OS samples compared with osteofibrous dysplasia. We subsequently demonstrated that GHR knockdown inhibited colony formation, promoted cell apoptosis and decreased the number of cells at G2/M phase in 143B and U2OS cells. Furthermore, knockdown of GHR inhibited tumor growth in vivo. Together, these findings indicate that GHR modulates cell proliferation and metastasis through the phosphoinositide 3-kinase/AKT signaling pathway and may be suitable for use as a putative biomarker of OS.

Undifferentiated Pleomorphic Sarcoma: Long-Term Follow-Up from a Large Institution.

PURPOSE: Our study aimed to describe the clinical features of undifferentiated pleomorphic sarcoma (UPS) and identify the predictors of poor outcomes. PATIENTS AND METHODS: The clinicopathological variables and treatment strategies of 100 UPS patients who underwent surgical resections at a single institution between November 2004 and July 2016 were reviewed. Kaplan-Meier and Cox regression method were conducted for survival analysis. RESULTS: The median follow-up time was 94 months (range, 1.5-154 months). R0 resection was applied for 72 cases, and the median tumor size was 5.75cm (range, 1-30cm). Tumor grades of 45 patients were intermediate grade (G2), and 54 patients were with advanced stage (stage III/IV). Twenty-seven patients presented with tumors involving important structures, in which the nerve was the most frequently invaded structure (n=12). During the follow-up, 40 patients suffered from postoperative local recurrence, and distant metastasis was observed in 25 patients which mainly metastasized to the lung (n=14). The 5-year OS rate, 5-year LRFS rate, and 5-year MFS rate was 53%, 55%, and 70%, respectively. Multivariate analysis revealed that tumor presentation, tumor size, and important structures involved (p=0.033, p=0.004, and p=0.033, respectively) were independent prognostic factors associated with OS. Meanwhile, age, resection quality and tumor grade were independent prognostic factors for LRFS (p=0.033, p=0.045, and p=0.007, respectively) and tumor depth was significantly associated with MFS (p=0.050) in multivariate analysis. CONCLUSION: Primary treatment of UPS should be conducted by experts in large sarcoma center. Wide surgical margin provides sufficient control of the disease recurrence.

Changes in the tumor immune microenvironment in resected recurrent soft tissue sarcomas.

BACKGROUND: Little is known about how the tumor immune microenvironment (TIME) is modulated in recurrent soft tissue sarcomas (STS). METHODS: We evaluated CD8+ T cells, CD20+ B cells, Foxp3+ regulatory T cells (Tregs), and programmed cell death ligand 1 (PD-L1) in 72 paired pre-recurrent (1st resected) versus post-recurrent (2nd resected) STS by immunohistochemistry. Correlations with time to recurrence and prognosis were determined. RESULTS: We found that CD8, PD-L1, CD20, and Foxp3-positive cell counts changed in post-recurrent STS. PD-L1-positive tumor cell and lymphocyte counts increased in post-recurrent STS, whereas CD8+ T cell counts decreased. Changes in CD8+ T cell, CD20+ B cell, and PD-L1+ lymphocyte counts were associated with the time interval between surgeries. At admission, fewer CD8+ T cells were detected in patients with relapse than in newly diagnosed patients. Furthermore, post-recurrent STS with fewer CD8+ T cells compared with pre-recurrent STS were more likely to exhibit re-recurrence. The change in CD8+ T cells was positively associated with overall survival. In multivariate analyses, a decrease in CD8+ T cell counts in post-recurrent STS was an independent unfavorable prognostic factor. CONCLUSIONS: The TIME differs between pre-recurrent STS and post-recurrent STS. The variation in CD8+ T cells and PD-L1 positivity may have essential roles during tumor relapse and provides a basis for determining therapeutic strategies.

Identification of Novel Fusion Transcripts in Undifferentiated Pleomorphic Sarcomas by Transcriptome Sequencing.

BACKGROUND/AIM: Undifferentiated pleomorphic sarcoma (UPS) is an aggressive mesenchymal neoplasm characterized by chromosomal instability. The aim of this study was to identify fusion events involved in UPS. MATERIALS AND METHODS: Transcriptome sequencing was performed to search for new fusion genes in 19 UPS samples, including two paired recurrent (R) and re-recurrent (RR) samples. RESULTS: A total of 66 fusion genes were detected. Among them, 10 novel fusion genes were further confirmed by reverse transcription polymerase chain reaction (RT-PCR) and Sanger sequencing. Retinoblastoma (RB1) fusions (2 cases) were the most recurrent fusion genes. The gene fusions RB1-RNASEH2B, RB1-FGF14-AS1, and E2F6-FKBP4 were correlated with the Rb/E2F pathway. Pseudogenes were involved in the formation of the gene fusions CIC-DUX4L8 and EIF2AK4-ANXA2P2. Importantly, targetable gene fusions (PDGFRA-MACROD2 and NCOR1-MAP2K1) were detected in UPS. CONCLUSION: Screening for the presence of fusion transcripts will provide vital clues to the understanding of genetic alterations and the finding of new targeted therapies for UPS.

RDM1 promotes neuroblastoma growth through the RAS-Raf-MEK-ERK pathway.

Neuroblastoma (NB) is an aggressive cancer that originates in the sympathetic nervous system and primarily affects children. Here, we show that high levels of RAD52 motif containing 1 (RDM1; a protein with similarities to RAD52, which is important for double-strand DNA repair) are associated with poor clinical outcomes for NB. In addition, RDM1-/- cells exhibited increased sensitivity to cisplatin, a common chemotherapy drug, and disruption of RDM1 suppressed NB cell proliferation. We also report that loss of RDM1 augmented cell apoptosis and induced cell cycle arrest, and that stable knockdown of RDM1 significantly inhibited NB tumor growth in a xenograft mouse model. Importantly, we identified that RDM1 promoted cell proliferation via the RAS-Raf-mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) signaling pathway. In conclusion, the current study demonstrates a correlation between DNA damage regulator RDM1 and the oncogenic RAS-Raf-MEK-ERK pathway in NB.

Prognostic significance of pretreatment lymphocyte/monocyte ratio in retroperitoneal liposarcoma patients after radical resection.

BACKGROUND: The aim of this study was to evaluate the prognostic value of pretreatment inflammatory biomarkers in retroperitoneal liposarcoma (RPLS) patients after radical resection. PATIENTS AND METHODS: One hundred patients with RPLS who underwent radical resection between September 2004 and October 2010 at Fudan University Shanghai Cancer Center were included in this study. Laboratory tests of peripheral blood were sampled before surgery. The optimal cutoff values of systemic inflammatory markers were defined by receiver-operating curve analyses. Curves of disease-free survival (DFS) and overall survival (OS) were obtained by the Kaplan-Meier method. Cox proportional hazards regression modeling was used to perform univariate and multivariate analyses. RESULTS: The median follow-up time was 53 months. The median DFS and OS were 27 and 86 months, respectively. On the basis of the optimal cutoff value of 3, 24 patients were classified into low lymphocyte/monocyte ratio (LMR) group and 76 patients into high LMR group. In univariate analysis, low LMR group had significantly shorter DFS (P<0.001) and OS (P<0.001) compared to high LMR group. In multivariate analysis, low LMR was demonstrated as an independent negative prognostic factor for both DFS (HR=2.854, 95% CI=1.392-5.851, P=0.004) and OS (HR=3.897, 95% CI=1.681-9.033, P=0.002). CONCLUSION: Pretreatment LMR is a useful prognostic marker in RPLS patients after radical resection.