Adenovirus expressing dual c-Met-specific shRNA exhibits potent antitumor effect through autophagic cell death accompanied by senescence-like phenotypes in glioblastoma cells

c-Met, a cognate receptor tyrosine kinase of hepatocyte growth factor, is overexpressed and/or mutated in number of tumors. Therefore, abrogation of c-Met signaling may serve as potential therapeutic targets. In this study, we generated Ads expressing single shRNA specific to c-Met (shMet) (dl/shMet4 and dl/shMet5) or dual shRNAs specific to c-Met (dl/shMet4+5); and examined the therapeutic potential of these newly engineered Ads in targeting c-Met, and delineated their mechanism of action in vitro and in vivo. Ads expressing shMet induced knock-down in c-Met, and phenotypically resulted in autophagy-like features including appearance of membranousvacuoles, formation of acidic vesicular organelles, and cleavage and recruitment of microtubule-associated protein1 light chain 3 to autophagosomes. Ads expressing shMet also suppressed Akt phosphorylation and increased number of senescence-related gene products including SM22, TGase II, and PAI-1. These changes resulted in inhibition of cell proliferation and G₂/M arrest of U343 cells. In vivo, intratumoral injection with dl/shMet4+5 resulted in a significant reduction of tumor growth with corresponding increasing overall survival. Histopathological analysis of these treated tumors revealed that Atg5 was highly up-regulated, indicating the therapeutic induction of autophagy. In sum, these results reveal that autophagic cell death induced by shMet-expressing Ads provide a novel strategy for targeting c-Met-expressing tumors through non-apoptotic mechanism of cell death.     

Single-site robotic surgery in gynecologic cancer: a pilot study

Objective

To discuss the feasibility of single-site robotic surgery for benign gynecologic tumors and early stage gynecologic cancers.

Methods

In this single institution, prospective analysis, we analyzed six patients who had undergone single-site robotic surgery between December 2013 and August 2014. Surgery was performed using the da Vinci Si Surgical System. Patient characteristics and surgical outcomes were analyzed.

Results

Single-site robotic surgery was performed successfully in all six cases. The median patient age was 48 years, and the median body mass index was 25.5 kg/m² (range, 22 to 33 kg/m²). The median total operative time was 211 minutes, and the median duration of intracorporeal vaginal cuff suturing was 32 minutes (range, 22 to 47 minutes). The median duration of pelvic lymph node dissection was 31 minutes on one side and 27 minutes on the other side. Patients'' postoperative courses were uneventful. The median postoperative hospital stay was 4 days. No postoperative complications occurred.

Conclusion

When used to treat benign gynecologic tumors and early stage gynecologic cancers, the single-site da Vinci robotic surgery is feasible, safe, and produces favorable surgical outcomes.     

Association between Extracellular Material and Biofilm Formation in Response to Sodium Hypochlorite by Clinical Isolates of Enterococcus faecalis

Introduction

Extracellular material (ECM) surrounding Enterococcus faecalis may play a role in increasing resistance to environmental stresses. Our aim was to determine ECM levels in response to subminimal inhibitory concentrations of sodium hypochlorite (sub-MIC/NaOCl) or anaerobic growth and determine the impact on biofilm development.

High-energy proton irradiation damage on two-dimensional hexagonal boron nitride

The dielectric layer, which is an essential building block in electronic device circuitry, is subject to intrinsic or induced defects that limit its performance. Nano-layers of hexagonal boron nitride (h-BN) represent a promising dielectric layer in nano-electronics owing to its excellent electronic and thermal properties. In order to further analyze this technology, two-dimensional (2D) h-BN dielectric layers were exposed to high-energy proton irradiation at various proton energies and doses to intentionally introduce defective sites. A pristine h-BN capacitor showed typical degradation stages with a hard breakdown field of 10.3 MV cm⁻¹, while h-BN capacitors irradiated at proton energies of 5 and 10 MeV at a dose of 1 × 10¹³ cm⁻² showed lower hard breakdown fields of 1.6 and 8.3 MV cm⁻¹, respectively. Higher leakage currents were observed under higher proton doses at 5 × 10¹³ cm⁻², resulting in lower breakdown fields. The degradation stages of proton-irradiated h-BN are similar to those of defective silicon dioxide. The degradation of the h-BN dielectric after proton irradiation is attributed to Frenkel defects created by the high-energy protons, as indicated by the molecular dynamics simulation. Understanding the defect-induced degradation mechanism of h-BN nano-layers can improve their reliability, paving the way to the implementation of 2D h-BN in advanced micro- and nano-electronics.

The dielectric layer, which is an essential building block in electronic device circuitry, is subject to intrinsic or induced defects that limit its performance.     

Can preoperative MR imaging predict optic nerve invasion of retinoblastoma?

Purpose

To evaluate the accuracy of pre-operative MRI for the detection of optic nerve invasion in retinoblastoma.

Materials and methods

Institutional review board approval and informed consent were waived for this retrospective study. A total of 41 patients were included. Inclusion criteria were histologically proven retinoblastoma, availability of diagnostic-quality preoperative MR images acquired during the 4 weeks before surgery, unilateral retinoblastoma, and normal-sized optic nerve. Two radiologists retrospectively reviewed the MR images independently. Five imaging findings (diffuse mild optic nerve enhancement, focal strong optic nerve enhancement, optic sheath enhancement, tumor location, and tumor size) were evaluated against optic nerve invasion of retinoblastoma. The predictive performance of all MR imaging findings for optic nerve invasion was also evaluated by the receiver operating characteristic curve analysis.

Results

Optic nerve invasion was histopathologically confirmed in 24% of study population (10/41). The differences in diffuse mild enhancement, focal strong enhancement, optic sheath enhancement, and tumor location between patients with optic nerve invasion and patients without optic nerve invasion were not significant. Tumor sizes were 16.1 mm (SD: 2.2 mm) and 14.9 mm (SD: 3.6 mm) in patients with and without optic nerve involvement, respectively (P = 0.444). P-Values from binary logistic regression indicated that all five imaging findings were not significant predictors of tumor invasion of optic nerve. The AUC values of all MR imaging findings for the prediction of optic nerve invasion were 0.689 (95% confidence interval: 0.499–0.879) and 0.653 (95% confidence interval: 0.445–0.861) for observer 1 and observer 2, respectively.

Conclusion

Findings of MRI in patients with normal-sized optic nerves have limited usefulness in preoperatively predicting the presence of optic nerve invasion in retinoblastoma.     

A proposal for combined MRI and PET/CT interpretation criteria for preoperative nodal staging in non-small-cell lung cancer

Objectives

To determine the positive reading criteria for malignant nodes when interpreting combined MRI and PET/CT images for preoperative nodal staging in non-small-cell lung cancer (NSCLC).

Methods

Forty-nine patients with biopsy-proven NSCLC underwent both PET/CT and thoracic MRI [diffusion weighted imaging (DWI)]. Each nodal station was evaluated for the presence of metastasis by applying either inclusive (positive if either one read positive) or exclusive (positive if both read positive) criteria in the combined interpretation of PET/CT and MRI. Nodal stage was confirmed pathologically. The combined diagnostic accuracy of PET/CT and MRI was determined on per-nodal station and per-patient bases and compared with that of PET/CT alone.

Results

In 49 patients, 39 (19%) of 206 nodal stations harboured malignant cells. Out of 206 nodal stations, 186 (90%) had concordant readings, while the rest (10%) had discordant readings. Inclusive criteria of combined PET/CT and MRI helped increase sensitivity for detecting nodal metastasis (69%) compared with PET/CT alone (46%; P?=?0.003), while specificity was not significantly decreased.

Conclusion

Inclusive criteria in combined MRI and PET/CT readings help improve significantly the sensitivity for detecting nodal metastasis compared with PET/CT alone and may decrease unnecessary open thoracotomy. Key Points ? Combined interpretation of MRI and PET/CT enhances the detection of nodal metastasis. ? Inclusive criteria of combined MRI/PET/CT improved the sensitivity for detecting nodal metastasis. ? Combined interpretation of MRI and PET/CT may reduce unnecessary open thoracotomies.     

Hypervascular hepatic nodules in childhood cancer survivors: clinical and imaging features

AimThe aim was to review the clinical and imaging features of hypervascular hepatic nodule (HHN) in childhood cancer survivors.Materials and methodsWe retrospectively reviewed 11 pediatric patients (female:male, 7:4; age range, 4.0–12.3 years) who had HHNs detected by surveillance computed tomography (CT) after treatment of a malignant solid tumor and subsequently followed by serial imaging without evidence of recurrent malignancy. The lesions were analyzed in terms of number, size, location, CT and ultrasonographic (US) features, and changes in background liver. In addition, clinical features were investigated along with follow-up changes of HHNs by imaging monitoring.ResultsTime between initial diagnosis of malignancy and HHN occurrence ranged from 3.2 to 8.5 years (median, 5.8 years). Ten patients had received high-dose chemotherapy and autologous stem cell transplantation for advanced neuroblastoma. A total of 22 nodules were detected, being multiple in six patients and measuring 0.5–3.0 cm in size. At sequential postcontrast CT, nodules demonstrated moderate to strong enhancement during the earlier phase and were isoattenuated during the later phase. On US, they appeared as hypo- or isoechoic lesions. During follow-up, 11 nodules (50%) regressed, 6 (27%) progressed, and 5 (23%) remained stable. Additional HHNs were noted in four patients during follow-up.ConclusionChildhood cancer survivors are at risk of developing HHNs, which are often multiple and small, years after completing chemotherapy. They are nonaggressive and tend to have a benign course, making conservative management reasonable.