Additional file 1: of Phase I/II dose-finding study of nanoparticle albumin-bound paclitaxel (nabÂŽ-Paclitaxel) plus Cisplatin as Treatment for Metastatic Nasopharyngeal Carcinoma

Raw data that supports the conclusion. (XLS 763 kb

Ultrasound-mediated nanobubble destruction (UMND) facilitates the delivery of A10-3.2 aptamer targeted and siRNA-loaded cationic nanobubbles for therapy of prostate cancer

<p>The Forkhead box M1 (FoxM1) transcription factor is an important anti-tumor target. A novel targeted ultrasound (US)-sensitive nanobubble that is likely to make use of the physical energy of US exposure for the improvement of delivery efficacy to target tumors and specifically silence FoxM1 expression appears as among the most potential nanocarriers in respect of drug delivery. In this study, we synthesized a promising anti-tumor targeted FoxM1 siRNA-loaded cationic nanobubbles (CNBs) conjugated with an A10-3.2 aptamer (siFoxM1-Apt-CNBs), which demonstrate high specificity when binding to prostate-specific membrane antigen (PSMA) positive LNCaP cells. Uniform nanoscaled siFoxM1-Apt-CNBs were developed using a thin-film hydration sonication, carbodiimide chemistry approaches, and electrostatic adsorption methods. Fluorescence imaging as well as flow cytometry evidenced the fact that the siFoxM1-Apt-CNBs were productively developed and that they specifically bound to PSMA-positive LNCaP cells. siFoxM1-Apt-CNBs combined with ultrasound-mediated nanobubble destruction (UMND) significantly improved transfection efficiency, cell apoptosis, and cell cycle arrest <i>in vitro</i> while reducing FoxM1 expression. <i>In vivo</i> xenografts tumors in nude-mouse model results showed that siFoxM1-Apt-CNBs combined with UMND led to significant inhibition of tumor growth and prolonged the survival of the mice, with low toxicity, an obvious reduction in FoxM1 expression, and a higher apoptosis index. Our study suggests that siFoxM1-Apt-CNBs combined with UMND might be a promising targeted gene delivery strategy for therapy of prostate cancer.</p

Multi-Targeted Antiangiogenic Tyrosine Kinase Inhibitors in Advanced Non-Small Cell Lung Cancer: Meta-Analyses of 20 Randomized Controlled Trials and Subgroup Analyses

<div><p>Background</p><p>Multi-targeted antiangiogenic tyrosine kinase inhibitors (MATKIs) have been studied in many randomized controlled trials (RCTs) for treatment of advanced non-small cell lung cancer (NSCLC). We seek to summarize the most up-to-date evidences and perform a timely meta-analysis.</p><p>Methods</p><p>Electronic databases were searched for eligible studies. We defined the experimental arm as MATKI-containing group and the control arm as MATKI-free group. The extracted data on objective response rates (ORR), disease control rates (DCR), progression-free survival (PFS) and overall survival (OS) were pooled. Subgroup and sensitivity analyses were conducted.</p><p>Results</p><p>Twenty phase II/III RCTs that involved a total of 10834 participants were included. Overall, MATKI-containing group was associated with significant superior ORR (OR 1.29, 95% CI 1.08 to 1.55, <i>P</i> = 0.006) and prolonged PFS (HR 0.83, 0.78 to 0.90, <i>P</i> = 0.005) compared to the MATKI-free group. However, no significant improvements in DCR (OR 1.08, 1.00 to 1.17, <i>P</i> = 0.054) or OS (HR 0.97, 0.93 to 1.01, P = 0.106) were observed. Subgroup analyses showed that the benefits were predominantly presented in pooled results of studies enrolling previously-treated patients, studies not limiting to enroll non-squamous NSCLC, and studies using MATKIs in combination with the control regimens as experimental therapies.</p><p>Conclusions</p><p>This up-to-date meta-analysis showed that MATKIs did increase ORR and prolong PFS, with no significant improvement in DCR and OS. The advantages of MATKIs were most prominent in patients who received a MATKI in combination with standard treatments and in patients who had previously experienced chemotherapy. We suggest further discussion as to the inclusion criteria of future studies on MATKIs regarding histology.</p></div

Meta-analyses of MATKIs-containing regimens versus MATKIs-free regimens.

<p>A, ORR; B, DCR; C, PFS; D, OS.</p

Multivariate Cox’s proportional hazards model analyses of survival and bone metastasis (BMT).

<p>Multivariate Cox’s proportional hazards model analyses of survival and bone metastasis (BMT).</p

Flow chart of study selection.

<p>Flow chart of study selection.</p

The NSCLC sections were divided into three groups based on the blood vessel density and nucleolin expression.

<p>The tumor blood vessels and nucleolin were stained with anti-CD31 (green) and anti-nucleolin (red), respectively. Nuclei were stained with DAPI (blue). Representative images from the three groups were shown here. (A) CD31^hiNCL^hi, (B) CD31^hiNCL^lo, (C) CD31^loNCL^lo. Scale bar, 50 µm.</p

Univariate analyses of DFS and OS according to the expression of CD31 and nucleolin in all patients and subgroups with clinicopathologic variables (Log-rank test).

<p>Univariate analyses of DFS and OS according to the expression of CD31 and nucleolin in all patients and subgroups with clinicopathologic variables (Log-rank test).</p

Kaplan-Meier plots of DFS according to the expression of CD31 and nucleolin in the entire cohort.

<p>HH: CD31^hiNCL^hi, HL: CD31^hiNCL^lo, and LL: CD31^loNCL^lo.</p

Subgroup analyses of each endpoint (number of studies or arms).

<p>A, ORR; B, DCR; C, PFS; D, OS.</p