Robotic Versus Thoracoscopic Sub-lobar Resection for Octogenarians with Clinical Stage IA Non-small Cell Lung Cancer: A Propensity Score-Matched Real-World Study.

BACKGROUND: Minimally invasive sub-lobectomy is sufficient in treating small early-stage non-small cell lung cancer (NSCLC). However, comparison of the feasibility and oncologic efficacy between robot-assisted thoracoscopic surgery (RATS) and video-assisted thoracoscopic surgery (VATS) in performing sub-lobectomy for early-stage NSCLC patients age 80 years or older is scarce. METHODS: Octogenarians with clinical stage IA NSCLC (tumor size, ≤ 2 cm) undergoing minimally invasive wedge resection or segmentectomy at Shanghai Chest Hospital from 2011 to 2020 were retrospectively reviewed from a prospectively maintained database. Propensity score-matching (PSM) with a RATS versus VATS ratio of 1:4 was performed. Perioperative and long-term outcomes were analyzed. RESULTS: The study identified 594 patients (48 RATS and 546 VATS patients), and PSM resulted in 45 cases in the RATS group and 180 cases in the VATS group. The RATS patients experienced less intraoperative bleeding (60 mL [interquartile range (IQR), 50-100 mL] vs. 80 mL [IQR, 50-100 mL]; P = 0.027) and a shorter postoperative hospital stay (4 days [IQR, 3-5 days] vs. 5 days [IQR, 4-6 days]; P = 0.041) than the VATS patients. The two surgical approaches were comparable concerning other perioperative outcomes and postoperative complications (20.00% vs. 26.11%; P = 0.396). Additionally, during a median follow-up period of 66 months, RATS and VATS achieved comparable 5-year overall survival (90.48% vs. 87.93%; P = 0.891), recurrence-free survival (83.37% vs. 83.18%; P = 0.782), and cumulative incidence of death. Further subgroup comparison also demonstrated comparable long-term outcomes between the two approaches. Finally, multivariate Cox analysis indicated that the surgical approach was not independently correlated with long-term outcomes. CONCLUSIONS: The RATS approach shortened the postoperative hospital stay, reduced intraoperative bleeding by a statistically notable but clinically insignificant amount, and achieved long-term outcomes comparable with VATS in performing sub-lobectomy for octogenarians with early-stage small NSCLC.

Fluorescence and colorimetric dual-mode multienzyme cascade nanoplatform based on CuNCs/FeMn-ZIF-8/PCN for detection of sarcosine.

It is critical to develop a highly efficient and sensitive method for detecting the biomarker sarcosine (SA) of prostate cancer due to its importance for men's health. In our work, a fluorescence (FL) and colorimetric dual-mode multienzyme cascade nanoplatform for SA detection was designed and constructed. CuNCs/FeMn-ZIF-8/PCN nanocomposites with high FL properties and peroxidase-like activity were successfully prepared by encapsulating copper nanoclusters (CuNCs) into FeMn-ZIF-8 and then loaded onto P-doped graphitic carbon nitride (PCN). Furthermore, the nanocomposites served as carriers for the immobilization of sarcosine oxidase (SOX) to construct a high-efficiency dual-mode multienzyme cascade nanoplatform CuNCs/SOX@FeMn-ZIF-8/PCN for the detection of SA. The intermediate H2O2 generated in the cascade caused the FL quenching of nanocomposites and the discoloration of 3,3',5,5'-tetramethylbenzidin. The linear ranges for SA detection in the dual-mode system were 1-100 µM (FL) and 1-200 µM (colorimetric), with detection limits of 0.34 and 0.59 µM, respectively. This nanoplatform exhibited notable repeatability, specificity, and stability, making it suitable for detecting sarcosine in real human urine samples. Therefore, this dual-mode multienzyme cascade nanoplatform would have a potential applicative prospect for detecting SA and other biomarkers in real clinical samples.

Non-linear modifications enhance prediction of pathological response to pre-operative PD-1 blockade in lung cancer: A longitudinal hybrid radiological model.

Major pathologic remission (MPR, residual tumor <10%) is a promising clinical endpoint for prognosis analysis in patients with lung cancer receiving pre-operative PD-1 blockade therapy. Most of the current biomarkers for predicting MPR such as PD-L1 and tumor mutation burden (TMB) need to be obtained invasively. They cannot overcome the spatiotemporal heterogeneity or provide dynamic monitoring solutions. Radiomics and artificial intelligence (AI) models provide a practical tool enabling non-invasive follow-up observation of tumor structural information through high-throughput data analysis. Currently, AI-based models mainly focus on the single baseline scan or pipeline, namely sole radiomics or deep learning (DL). This work merged the delta-radiomics based on the slope of classic radiomics indexes within a time interval and the features extracted by deep networks from the subtraction between the baseline and follow-up images. The subtracted images describing the tumor changes were based on the transformation generated by registration. Stepwise optimization of components was performed by repeating experiments among various combinations of DL networks, registration methods, feature selection algorithms, and classifiers. The optimized model could predict MPR with a cross-validation AUC of 0.91 and an external validation AUC of 0.85. A core set of 27 features (eight classic radiomics, 15 delta-radiomics, one classic DL features, and three delta-DL features) was identified. The changes in delta-radiomics indexes during the treatment were fitted with mathematic models. The fitting results revealed that over half of the features were of non-linear dynamics. Therefore, non-linear modifications were made on eight features by replacing the original features with non-linear fitting parameters, and the modified model achieved an improved power. The dynamic hybrid model serves as a novel and promising tool to predict the response of lesions to PD-1 blockade, which implies the importance of introducing the non-linear dynamic effects and DL approaches to the original delta-radiomics in the future.

MTM-HCC at Previous Liver Resection as a Predictor of Overall Survival in Salvage Liver Transplantation.

OBJECTIVES: Salvage liver transplantation (sLT) is considered an effective method to treat hepatocellular carcinoma (HCC) recurrence. This multicenter research aimed to identify the prognostic factors associated with recurrence-free survival (RFS) and overall survival (OS) after sLT. MATERIAL AND METHODS: A retrospective analysis of 114 patients who had undergone sLT for recurrent HCC between February 2012 and September 2020 was performed. The baseline and clinicopathological data of the patients were collected. RESULTS: The 1-, 3-, and 5-year RFS rates after sLT were 88.9%, 75.2%, and 69.2%, respectively, and the OS rates were 96.4%, 78.3%, and 70.8%. A time from liver resection (LR) to recurrence < 1 year, disease beyond the Milan criteria at sLT and macrotrabecular massive (MTM)-HCC were identified as risk factors for RFS and were further identified as independent risk factors. A time from LR to recurrence < 1 year, disease beyond the Milan criteria at sLT and MTM-HCC were also risk factors for OS and were further identified as independent risk factors. CONCLUSIONS: Compared with primary liver transplantation (pLT), more prognostic factors are available from patients who had undergone LR. We suggest that in cases of HCC recurrence within 1 year after LR, disease beyond the Milan criteria at sLT and MTM-HCC patients, sLT should be used with caution.

Design, Synthesis, Biological Evaluation and Molecular Docking Studies of Quercetin-Linker-H2 S Donor Conjugates for the Treatment of Diabetes and Wound Healing.

Based on the use of quercetin for treating diabetes and H2 S for promoting wound healing, a series of three quercetin-linker-H2 S donor conjugates was designed, synthesized and characterized by 1 H-NMR, 13 C-NMR and MS. Meanwhile, in vitro evaluation of these compounds was also researched by IR-HepG2 treatment experiment, MTT assay, scratch test and tubule formation experiment. The three compounds could be used to treat insulin resistance induced by high glucose and promote the proliferation of human umbilical vein endothelial cells, wound healing, and the formation of tubules in vitro under a high-glucose environment. Our results illustrate that these compounds could be used to treat diabetes and promote wound healing at the same time. Furthermore, molecular docking study results of the compounds were consistent with the evaluated biological activity. In vivo research of compounds is underway.

Competitive fluorescent immunoassay for the ultrasensitive determination of amyloid beta peptide1-42 based on Ag@SiO2@N, S-GQD nanocomposites.

A competitive fluorescent immunoassay is described for the ultrasensitive determination of amyloid beta peptide1-42 (Aß1-42), a biomarker for early diagnosis of Alzheimer's disease. N, S-doped graphene quantum dots (N, S-GQDs) were freely assembled on the surface of Ag@SiO2 nanoparticles to obtain a composite (Ag@SiO2@N, S-GQD nanocomposite), which was successfully prepared and characterized. By theoretical study, the optical properties of nanocomposites are improved compared with GQDs, due to the advantages of combining N, S co-doping and metal-enhanced fluorescence (MEF) effect of Ag NPs. In addition, Aß1-42 was modified by Ag@SiO2@N, S-GQDs to prepare a probe with high photoluminescence properties (Ag@SiO2@N, S-GQDs-Aß1-42). In the presence of Aß1-42, a competitive reaction towards anti-Aß1-42 fixed on the ELISA plate was proceeded between Aß1-42 and Ag@SiO2@N, S-GQDs-Aß1-42 by specific capture of antigen-antibody. The emission peak of Ag@SiO2@N, S-GQDs-Aß1-42 (400 nm emission) was used for the quantitative determination of Aß1-42. Under the optimal conditions, the fluorescent immunoassay exhibited a linear range of 0.32 pg·mL-1-5 ng·mL-1 with a detection limit of 0.098 pg·mL-1. The results show that the immunoassay has good analytical ability and can provide a new method for the clinical determination of Aß1-42.

Selective Delivery of Tofacitinib Citrate to Hair Follicles Using Lipid-Coated Calcium Carbonate Nanocarrier Controls Chemotherapy-Induced Alopecia Areata.

Chemotherapy-induced alopecia (CIA) is one of the common side effects in cancer treatment. The psychological distress caused by hair loss may cause patients to discontinue chemotherapy, affecting the efficacy of the treatment. The JAK inhibitor, Tofacitinib citrate (TFC), showed huge potential in therapeutic applications for treating baldness, but the systemic adverse effects of oral administration and low absorption rate at the target site limited its widespread application in alopecia. To overcome these problems, we designed phospholipid-calcium carbonate hybrid nanoparticles (PL/ACC NPs) for a topical application to target deliver TFC. The results proved that PL/ACC-TFC NPs showed excellent pH sensitivity and transdermal penetration in vitro. PL/ACC NPs offered an efficient follicular targeting approach to deliver TFC in a Cyclophosphamide (CYP)-induced alopecia areata mouse model. Compared to the topical application of TFC solution, PL/ACC-TFC NPs significantly inhibited apoptosis of mouse hair follicles and accelerated hair growth. These findings support that PL/ACC-TFC NPs has the potential for topical application in preventing and mitigating CYP-induced Alopecia areata.

A New 7-Azaindole Structure Analog: Molecular Docking, Synthesis and Preliminary Biological Activity in Vitro for Anticancer.

In this work, a series of 7-azaindole analogs were designed by the bioisosteric principle based on the pharmacodynamic parent nucleus. Moreover, 5-[(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl]-N-{[6-(trifluoromethyl)pyridin-3-yl]methyl}pyrimidin-2-amine (compound P1) with the strongest interaction with colony-stimulating factor 1 receptor (CSF-1R) was screened by molecular docking. Compound P1 was successfully prepared by the six-step reaction with HPLC purity of 99.26 % and characterized by 1 H-NMR and ESI-MS spectra. In vitro bioactivity study showed that compound P1 appeared the cytotoxicity to MCF-7 and A549 cells, especially to HOS cells (IC50 =88.79±8.07 nM), while it had lower toxicity to normal L929 cells (IC50 =140.49±8.03 µM). In addition, compound P1 could induce HOS cell death by apoptosis and blocking the G0/G1 phase at nanomolar concentrations. The obtained results indicated that compound P1 might be a promising candidate compound for anticancer drug.

Enhancement of anthocyanin and chromatic profiles in 'Cabernet Sauvignon' (Vitis vinifera L.) by foliar nitrogen fertilizer during veraison.

BACKGROUND: The influence of foliar nitrogen fertilizer during veraison (FNFV) on anthocyanin accumulation and chromatic characteristics of 'Cabernet Sauvignon' grapes over two seasons was investigated. RESULTS: Urea and phenylalanine fertilizers (TU and TP, respectively) and a control were sprayed three times at veraison. In 2018, TU displayed a significant enhancement in total individual anthocyanin content and a* and Cab * profiles. In 2019, FNAV significantly improved the content of total non-acylated, acylated anthocyanin and total individual anthocyanin, and the profiles of L*, a* and Cab *, except a* in TU. The whole process from phenylalanine variation to anthocyanin accumulation in grape skins was analyzed. On the whole, after the first FNFV to harvest, the increase in phenylalanine metabolism, abscisic acid content, effects of PAL (Phenylalanine ammonia lyase), UFGT (UDP glucose-flavonoid 3-O-glucosyltransferase) and transcript concentrations of VvPAL and VvUFGT involved in anthocyanin biosynthesis were also strong evidence explaining the increased anthocyanin and chromatic profiles in 2019. CONCLUSION: Overall, FNFV for nitrogen-deficient grapevines could significantly improve grape color, especially in the 2019 veraison with a proper climate. © 2021 Society of Chemical Industry.

Hyaluronic acid-functionalized redox responsive immunomagnetic nanocarrier for circulating tumor cell capture and release.

Detection of circulating tumor cells (CTCs) in peripheral blood holds significant insights for cancer diagnosis, prognosis evaluation, and precision medicine. To efficiently capture and release CTCs with high viability, we reported the development of hyaluronic acid (HA)-functionalized redox responsive immunomagnetic nanocarrier (Fe3O4@SiO2-SS-HA). First, Fe3O4nanoparticles were prepared and modified with tetraethyl orthosilicate (TEOS), 3-mercaptopropyltrimethoxysilane (MPTMS) and 2,2'-dithiodipyridine (DDPy) to form the magnetic substrate (Fe3O4@SiO2-SSPy). Modified with targeted segment HA-functionalized L-cysteine ethyl ester hydrochloride (HA-Cys) via disulfide exchange reaction, the Fe3O4@SiO2-SS-HA was formed. The nanocarrier with prominent magnetic property, targeting ligand, and redox-sensitive disulfide linkages was able to specially capture MCF-7 cells with an efficiency of 92% and effectively release captured cells with an efficiency of 81.4%. Furthermore, the Fe3O4@SiO2-SS-HA could successfully be used for the capture of MCF-7 cells, and the captured cells could be diferntiated from the blood cells. Almost all of released tumor cells kept good viability and a robust proliferative capacity after being re-cultured. It is likely that the as-prepared nanocarrier will serve as a new weapon against CD44 receptor-overexpressed cancer cells.

CQMUH-011 mitigates autoimmune hepatitis via inhibiting the function of T lymphocytes.

CQMUH-011 is a modified adamantane sulfonamide compound, that inhibits macrophage proliferation and possesses anti-inflammatory properties. Here, fresh mouse splenocytes were obtained and stimulated with concanavalin A (ConA, 5 µg/ml) in vitro; and experimental autoimmune hepatitis (AIH) was induced by ConA (20 mg/kg, iv) in vivo, to clarify the protective effects of CQMUH-011 against AIH and its possible mechanisms. Our results demonstrated that CQMUH-011 pretreatment can dose-dependently inhibit the proliferation of splenocytes in vitro. In vivo, CQMUH-011 administration reduced the hepatic histopathological score and the infiltration of lymphocytes in the liver parenchyma; additionally, it downregulated the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and pro-inflammatory cytokines interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 in serum, as well as those of methane dicarboxylic aldehyde and myeloperoxidase in the liver tissues. It also down-regulated the expression of p-NF-κB and related proteins in the liver tissues. Furthermore, CQMUH-011 could maintain the balance of CD3+ CD4+ /CD3+ CD8+ and decrease the percentages of CD8+ CD69+ and CD4+ CD25+/- CD69+ T-cells in the splenocytes of ConA-challenged mice. Moreover, we found thatCD4+ CD25+/- CD69+ T-cells were significantly correlated with ALT levels, especially CD4+ CD25- CD69+ T-cells. In conclusion, CQMUH-011 exerts potential protective effects against ConA-induced hepatitis, which may be partially attributed to its inhibition of T cells, especially the suppression of the proliferation of CD4+ CD25- CD69+ and CD8+ CD69+ subsets in the spleen. CQMUH-011 also reduced the early apoptosis of lymphocytes in the thymus.

Long-term outcomes of multimodality management for parasagittal meningiomas.

PURPOSE: The aim of this study was to systematically analyze the clinical characteristics of a large cohort of parasagittal meningioma (PM) and to evaluate the patients' outcomes and best treatment strategies based on tumor features. METHODS: To minimize selection bias we performed a single-institutional review of PM with restricted criteria. One hundred and ninety-two consecutive patients who met criteria for inclusion were reviewed from 2003 to 2011 in our general hospital. RESULTS: A total of 131 cases (68.2%) were with WHO grade I, while grade II and grade III PMs constituted 40 (20.8%) and 21 cases (10.9%). Higher histological grade was associated with loss of trimethylation of H3K27 (P = 0.000). For WHO grade I PMs, GTR was significantly associated with a better PFS (P = 0.023); however, adjuvant radiotherapy did not benefit patients with STR (P = 0.215). For de novo high-grade (WHO grade II and III) PMs (n = 37), adjuvant radiotherapy was associated with a significantly longer OS (P = 0.013), while no difference was observed between GTR and STR (P = 0.654). In recurrent high-grade PM patients (n = 24), GTR combined with adjuvant radiotherapy increased PFS (P = 0.005). CONCLUSIONS: This study demonstrated that PMs were a heterogeneous group of tumors with a high proportion of high-grade tumors that often displayed aggressive clinical behaviors. Low-grade PM benefited from radical resection, whereas high-grade de novo PM did not. Adjuvant radiotherapy significantly prolonged OS for high-grade primary PM, but did not impact survival of patients with subtotally resected low-grade tumors. Long-term outcome of high-grade recurrent PMs was dismal. We thus show that extent of tumor resection, tumor grade and tumor recurrent status inform therapeutic decisions for PMs.

Options for the treatment of intrahepatic recurrent hepatocellular carcinoma: Salvage liver transplantation or rehepatectomy?

OBJECTIVE: To explore prognostic factors by comparing the efficacy of salvage liver transplantation (sLT) and rehepatectomy (RH) for the treatment of recurrent hepatocellular carcinoma after hepatectomy. METHODS: Clinical data were collected for 124 patients treated at our center from January 2012 to August 2018. The median follow-up time for the patients was 39 months. By analyzing the clinical data between the sLT group (46 cases) and RH group (78 cases), the factors affecting the prognosis of patients were compared. RESULTS: The proportion of alpha-fetoprotein (AFP) ≥ 100 µg/L in the recurrence group was significantly higher than that in the recurrence-free group (70.0% vs 22.2%, P = .014). The postoperative overall survival (OS) and recurrence-free survival (RFS) were better in the sLT group than in the RH group (81.2% vs 36.9%, P < .01; 77.1% vs 55.6%, P = .019). In the sLT group, the OS and RFS in the AFP < 100 µg/L group were superior to those in the AFP ≥ 100 µg/L group (P = .046 and P = .002). CONCLUSION: The sLT group had achieved better efficacy than RH group, but when AFP ≥ 100 µg/L, sLT did not achieve better efficacy than RH.

Paclitaxel/sunitinib-loaded micelles promote an antitumor response in vitro through synergistic immunogenic cell death for triple-negative breast cancer.

Chemotherapy-induced immunogenic cell death (ICD) may offer a strategy to improve the effect of the therapeutic treatment of triple-negative breast cancer (TNBC) by eliciting broad antitumor immunity. However, chemotherapy shows a limited therapeutic effect because of multi-drug resistance and the immunosuppressive tumor microenvironment (TME) of TNBC. The unique pharmacological actions of sunitinib (SUN) indicate its possible synergies with paclitaxel (PTX) to enhance chemo-immunotherapy for TNBC. Here, we prepared a co-delivery platform composed of poly(styrene-co-maleic anhydride) (SMA) via a self-assembly process for a combination of PTX and SUN, which was able to induce a higher synergistic ICD. The nanomicellar delivery of PTX and SUN loaded at an optimal ratio of 1:5 (PTX:SUN) presented the characteristics of an appropriate particle size, long-term stability, and time sequence release which synergistically promoted the apoptosis of MDA-MB-231 tumor cells. Moreover, we demonstrated that the combination of PTX and SUN could significantly induce a synergistic effect because it promoted an ICD response, improved tumor immunogenicity, and regulated immunosuppressive factors in the TME. Overall, PTX and SUN with synergistic effects entrapped in a self-assembly nano-delivery system could offer the potential for clinical applicationof a combination chemo-immunotherapy strategy to improve the effect of the therapeutic treatment of TNBC.

Co3O4 Nanosheets Preferentially Growing (220) Facet with a Large Amount of Surface Chemisorbed Oxygen for Efficient Oxidation of Elemental Mercury from Flue Gas.

Oxygen vacancies can capture and activate gaseous oxygen, forming surface chemisorbed oxygen, which plays an important role in the Hg0 oxidation process. Fine control of oxygen vacancies is necessary and a major challenge in this field. A novel method for facet control combined with morphology control was used to synthesize Co3O4 nanosheets preferentially growing (220) facet to give more oxygen vacancies. X-ray photoelectron spectroscopy (XPS) results show that the (220) facet has a higher Co3+/Co2+ ratio, leading to more oxygen vacancies via the Co3+ reduction process. Density functional theory (DFT) calculations confirm that the (220) facet has a lower oxygen vacancy formation energy. Furthermore, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) results suggest that Co3O4 nanosheets yield more defects during the synthesis process. These results are the reasons for the greater number of oxygen vacancies in Co3O4 nanosheets, which is confirmed by electron energy loss spectroscopy (EELS), Raman spectroscopy, and photoluminescence (PL) spectroscopy. Therefore, Co3O4 nanosheets show excellent Hg0 removal efficiency over a wide temperature range of 100-350 °C at a high gas hourly space velocity (GHSV) of 180 000 h-1. Additionally, the catalytic efficiency of Co3O4 nanosheets is still greater than 83%, even after 80 h of testing, and it recovers to its original level after 2 h of in situ thermal treatment at 500 °C.

Synthesis of gadolinium-based Bi2S3 nanoparticles as cancer theranostics for dual-modality computed tomography/magnetic resonance imaging-guided photothermal therapy.

Development of a safe, efficient and inexpensive multifunctional nanoplatform using a facile approach for multimodal imaging and therapeutic functions becomes more and more practically relevant but challenging. In this work, we demonstrated a novel nanocomposites (Bi2S3-Gd) for computed tomography (CT)/magnetic resonance (MR) imaging-guided photothermal therapy (PTT) for cancer in vitro. It was achieved by modification of hydrophobic Bi2S3 with a smart amphiphilic gadolinium-chelated ligand. The as-prepared nanocomposites composed of low-cost Bi2S3 and gadolinium complexes, showed high stability, excellent biocompatibility and good photostability. It was observed that Bi2S3-Gd nanocomposites can efficiently convert the NIR light into heat, and then suppressed the growth of tumor cells under NIR laser irradiation. Apart from serving as an effective photothermal agent, the as-prepared nanomaterials could induce an efficient contrast enhancement for both CT and MR imaging at low concentrations of Bi and Gd, rendering more accurate diagnosis. This work suggests the potential of Bi2S3-Gd nanomaterials as a novel multifunctional nanoplatform for CT/MR imaging-guided PTT for cancer.

BRAF peptide vaccine facilitates therapy of murine BRAF-mutant melanoma.

Approximately, 50% of human melanomas are driven by BRAF mutations, which produce tumors that are highly immunosuppressive and often resistant to vaccine therapy. We introduced lipid-coated calcium phosphate nanoparticles (LCP NPs) as a carrier to efficiently deliver a tumor-specific antigen, the BRAFV600E peptide, to drive dendritic cell (DC) maturation and antigen presentation in C57BL6 mice. The BRAF peptide vaccine elicited a robust, antigen-specific cytotoxic T cell response and potent tumor growth inhibition in a murine BRAF-mutant melanoma model. Advanced BRAF-specific immune response was illustrated by IFN-γ production assay and cytotoxic T lymphocyte (CTL) assay. Remodeling of immunosuppressive modules within the tumor microenvironment further facilitated CTL infiltration. Thus, using LCP NPs to deliver the BRAF peptide vaccine is a promising strategy for the BRAF-mutant melanoma therapy.

Clinical and prognostic features of spinal meningioma: a thorough analysis from a single neurosurgical center.

PURPOSE: The aim of this study was to thoroughly analyze the clinical characteristics of a large cohort of spinal meningioma (SM) from a single neurological center and identify risk factors associated with worse progression free survival and neurological function outcome. METHODS: Clinical information was retrieved from 483 SM and 9806 cranial meningioma cases who were operated in our center between 2003 and 2013. 194 SM patients who were followed at the main branch were used for prognostic analyses that included both recurrence free survival and neurological functions based on Modified McCormick scale (MMS). RESULTS: Females were predominant (P < 0.001). High grade tumors were not common (WHO grade II, 2.9%; grade III, 1.7%), while the clear cell subtype was frequent within grade II SMs (6/14, 42.9%). Macroscopic total resection was achieved in all SMs (Simpson grade I, 30.9%; grade II, 65.5%; grade III, 3.6%) with a low complications rate (4.6%) and provided neurological improvement in 80 patients (41.2%). Recurrence was seen in 9 cases (4.6%) and associated with high WHO grade, male, prior recurrence, and Simpson grade III. High WHO grade and high Ki-67 index were identified to be independent factors predictive of both neurological function deterioration and impaired post-operative neurological status. CONCLUSIONS: Our analysis of the largest SM cohort in scale from a single institution offers a comprehensive view of the clinical characteristics of surgically treated SM, revealing the distinct biology of SM in comparison to its cranial counterparts, and providing guidance to improve surgical management of SM.

H19 promotes pancreatic cancer metastasis by derepressing let-7's suppression on its target HMGA2-mediated EMT.

The long noncoding RNA (lncRNA) H19 has been recently characterized as an oncogenic lncRNA in some tumors. However, the role of H19 in pancreatic ductal adenocarcinoma (PDAC) remains unclear. In this study, we found that not only the levels of H19 was overexpressed in PDAC compared with adjacent normal tissues, but also H19 expression was upregulated remarkably in primary tumors which subsequently metastasized, compared to those did not metastasis. Subsequently, the efficacy of knockdown of H19 by H19-small interfering RNA (siRNA) was evaluated in vitro, and we found that downregulation of H19 impaired PDAC cell invasion and migration. We further demonstrated that H19 promoted PDAC cell invasion and migration at least partially by increasing HMGA2-mediated epithelial-mesenchymal transition (EMT) through antagonizing let-7. This study suggests an important role of H19 in regulating metastasis of PDAC and provides some clues for elucidating the lncRNA-miRNA functional network in cancer.

SUMO-specific protease 1 regulates pancreatic cancer cell proliferation and invasion by targeting MMP-9.

SUMOylation is a dynamic process which can be reversed by a family of sentrin/SUMO-specific protease (SENPs). Recently, SENP1, a member of SENPs family was shown to have a pro-oncogenic role in many types of cancer. Here, we showed that SENP1 was upregulated in pancreatic ductal adenocarcinoma (PDAC) tissues compared with adjacent normal tissues. Moreover, clinical data showed that SENP1 was positively associated with lymph node metastasis and TNM stage. Furthermore, knockdown of SENP1 by SENP1-siRNA inhibited pancreatic cancer cell proliferation, migration, and invasion, suggesting that SENP1 played an important role in PDAC progression and metastasis. Mechanistically, silencing of SENP1 results in downregulation of MMP-9, which is pivotal for PDAC cell growth and migration. Taken together, these results suggest that SENP1 may serve as a potential novel diagnostic and therapeutic target of PDAC.