Search

Lung cancer is the primary cause of cancer related deaths in the western world and smoking significantly increases the risk of developing lung cancer. Smoking enhances lung cancer initiation and progression. The effects of cigarette smoke on lung cancer are mediated by the presence of highly mutagenic substances, including nicotine, leading to mutations in oncogenes and tumor suppressor genes. An emerging pathway in cancer is the Notch signaling pathway which is essential for embryonic lung development and tissue homeostasis. The role of Notch signaling in lung cancer remains controversial and no studies have directly linked cigarette exposure to mutations in Notch. Therefore, we investigated the direct effect of Notch signaling pathways on cigarette-induced lung tumors and the correlation between smoking and mutations in Notch leading to altered downstream signaling. Human cell lines, mouse models and clinical lung cancer samples were utilized in this study. Cigarette-induced in vitro human lung cancer models and in vivo mouse models demonstrated strong effects of cigarette exposure on the Notch signaling pathway. Immunohistochemistry (IHC) of 50 clinical samples collected from smokers and non-smokers with and without lung cancer also demonstrated a link between smoking and changes in Notch signaling. Finally, 34 lung cancer samples analyzed through direct sequencing indicated smoking significantly increased small nucleotide polymorphisms (SNPs) in Notch 1 and 2 and specific SNPs significantly modulated expression levels of downstream signaling pathway molecules. Taken together, these results demonstrate a direct effect of smoking on the Notch signaling pathway leading to lung cancer initiation and progression., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Bone health requires regulation of homeostatic equilibrium between osteoblasts and osteoclasts. The over-activation of osteoclasts can disrupt bone metabolism, resulting in osteoporosis and other bone-loss diseases. Fullerenol, a polyhydroxy derivative of fullerene, exhibits excellent biocompatibility. Here we show that fullerenol nanoparticles exert two functions: inhibition of osteoclastic differentiation and blockage of pre-osteoclast fusion to restructure osteoclast maturation and function. Experimentally, the nanoparticles reduced pre-osteoclast migration and inhibited ruffled border formation to block their maturation. In addition, fullerenol dose-dependently restricted the differentiation of bone marrow macrophage cells (BMMs) to form osteoclasts following treatment with macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor (NF)-κB (RANKL) to activate NF-κB and mitogen activating protein kinase (MAPK) signaling pathways. It is possible that the very small size of fullerenol allows it to directly cross the cellular membrane to access the cytoplasm and regulate osteoclastogenesis from BMMs. Our results suggest that fullerenol could be used to treat bone-loss diseases such as osteoporosis.

Objective: The objective of this meta-analysis was to investigate the efficacy of extracorporeal shock wave therapy in the treatment of recalcitrant plantar fasciitis without local anesthesia., Methods: The Cochrane Library, EMBASE, PubMed, and Web of Science databases were searched from inception to September 2015 for randomized controlled trials comparing ESWT without local anesthesia versus placebo for treatment of plantar fasciitis in adults. The primary outcome was the 12-week post-intervention success rate of reducing the visual analog scale score by 60% from baseline at the first step in the morning, reducing the VAS score by 60% from baseline during daily activities, reducing the Roles and Maudsley score, reducing overall heel pain, and reducing pain after applying a force meter., Results: Nine studies were included in the meta-analysis. Compared with placebo, ESWT significantly improved the success rate of reducing overall heel pain, reducing the VAS score by 60% at the first step in the morning and during daily activities, improving the Roles and Maudsley score to excellent or good, and reducing heel pain after application of a pressure meter., Conclusions: ESWT seems to be particularly effective in relieving pain associated with RPF. ESWT should be considered when traditional treatments have failed., To Claim Cme Credits: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to (1) understand the recovery rates for nonsurgical treatment of plantar fasciitis, (2) understand the role of extracorporeal shockwave therapy (ESWT) in the treatment of recalcitrant plantar fasciitis, and (3) understand the indications to incorporate ESWT in the treatment plan of recalcitrant plantar fasciitis., Level: Advanced ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this activity for a maximum of 1.5 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Purpose: We evaluated differences in clinicopathological characteristics and oncologic outcomes between patients with upper tract urothelial carcinoma in mainland China and the United States., Materials and Methods: We retrospectively compiled clinicopathological and oncologic outcomes data on patients with upper tract urothelial carcinoma treated surgically at tertiary care medical facilities in the United States or China from 1998 to 2015. Baseline demographics, comorbidities and pathological features were evaluated. Oncologic end points, including intravesical recurrence and cancer specific survival, were obtained after excluding patients who received systemic chemotherapy. Multivariable Cox regression was performed to determine predictors of adverse oncologic outcomes for each country., Results: A total of 775 patients with upper tract urothelial carcinoma were identified, including 451 in China and 324 in the United States. Median followup was 42 months. American patients were more frequently male (65% vs 44%) and smokers (79% vs 18%), and had a worse mean ASA® (American Society of Anesthesiologists®) score (2.7 vs 2.2) and prior bladder cancer (41% vs 4%, all p <0.001). Chinese patients more often had preoperative hydronephrosis (56% vs 40%), high grade pathology (98% vs 77%), muscle invasion (64% vs 38%) and nodal metastases (26% vs 6%, all p <0.001). American patients had worse overall survival on Kaplan-Meier analysis (p = 0.049). However, country of origin did not predict local relapse or cancer specific survival., Conclusions: Patient and disease characteristics of upper tract urothelial carcinoma differed between the Chinese and American cohorts. Chinese patients appeared relatively healthier at presentation but more often exhibited adverse pathological features. While evaluation and management patterns may account for these variations, the pathological findings may reflect a differential underlying pathogenesis of disease. Additional study is warranted to further characterize these differences., (Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: This study aimed to identify the optimal extracorporeal shock wave (ESW) intensity and to investigate its effect on subchondral bone rebuilt in vivo and Wnt5a/Ca 2+ signaling in vitro using an osteoarthritis (OA) rat model and bone marrow mesenchymal stem cells (BMMSCs), respectively., Methods: OA rats treated with (OA + ESW group) or without (OA group) ESW ( n = 12/group) were compared with healthy controls (control group, n = 12). Gait patterns and subchondral trabecular bone changes were measured. Western blot and quantitative real-time polymerase chain reaction detected protein expression and gene transcription, respectively., Results: The gait disturbances of OA + ESW group were significantly improved compared with the OA group at 6th and 8th weeks. The micro-CT analysis indicated that the BMD, BSV/BV, BV/TV, Tr.S, and Tr.Th are significantly different between OA group and OA + ESW group. Expression of Wnt5a was increased rapidly after ESW treatment at 0.6 bar and peaked after 30 min., Conclusions: ESW were positive for bone remodeling in joint tibial condyle subchondral bone of OA rat. ESW prevented histological changes in OA and prevented gait disturbance associated with OA progression. Optimal intensity of ESW induced changes in BMMSCs via activation of the Wnt5a/Ca 2+ signaling pathway.

The oncological outcomes of upper tract urothelial carcinoma (UTUC) and bladder cancer (BC) in patients treated with radical surgeries remains controversial. A retrospective analysis of the clinicopathologicla data of 228 consecutive UTUC patients and 174 BC patients treated with radical surgeries from 2000 to 2012 at a high-volume center in China was conducted. Kaplan-Meier method and Cox regression were used to compare overall survival (OS) and cancer-specific survival (CSS) and to find prognostic factors. In this cohort of patients, BC were associated with male sex (P<0.001), multifocality (P<0.001), positive lymph node (P=0.002), no hydronephrosis (P<0.001) and open surgical approach (P<0.001). UTUC have statistically significant better 5-year CSS rate (61.0% vs. 49.8%, P=0.008) and OS rate (58.3% vs. 37.4%, P<0.001) than BC. Bladder tumor location (UTCU vs. BC: hazard ratio (HR)=0.703 and HR=0.462) and positive lymph node status (HR=1.919 and HR=1.667) were independent risk factors of cancer-specific death and overall mortality, respectively. Our data suggest that locally invasive urothelial carcinomas (UC) behave differently in the upper and lower urinary tracts. UTUC has a better prognosis than BC when stage and grade are considered simultaneously and lymph node involvement has significant influences on clinical outcomes of urothelial carcinoma., Competing Interests: Disclosure of conflict of interest None.

Malignant peripheral nerve sheath tumor (MPNST) is a rare and aggressive soft tissue sarcoma for which effective treatments have not yet been established due to poor understanding of its pathogenesis. Our previous study indicated that miR-210-mediated Ephrin-A3 (EFNA3) promotion of proliferation and invasion of MPNST cells plays an important role in MPNST tumorigenesis and progression. The purpose of the present study was to further investigate the roles of EFNA3 in MPNST. Constructed transcription activator-like effector nucleases (TALENs) and lentiviral vectors were transfected into MPNST ST88-14 (NF1 wild-type) and sNF96.2 (NF1 mutant type) cell lines to obtain gain- and loss-of-function cell lines for the EFNA3 function study. The results showed that the knockout of ENFA3 increased cellular viability and invasiveness of the MPNST cells. However, the adhesion ability of MPNST cells was enhanced or inhibited when EFNA3 was overexpressed or knocked out, respectively. It was also observed that knockout of EFNA3 significantly decreased the expression of phosphorylated FAK (p-FAK) and the tumor necrosis factor α (TNF-α) compared to that in the control cells, yet the expression of phosphatidylinositol 3-kinase (PI3K), GTPase, integrins, vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1α (HIF-α) increased significantly. Inversely, overexpression of EFNA3 significantly increased the expression of p-FAK and TNF-α compared to that in the control cells, yet the expression of PI3K, GTPase, integrins, VEGF and HIF-α decreased significantly. The results indicated that EFNA3 serves as a tumor suppressor in MPNST cells and it may play a critical role in the focal adhesion kinase (FAK) signaling and VEGF-associated tumor angiogenesis pathway. These findings may not only facilitate the better understanding of MPNST pathogenesis, but also suggest EFNA3 as a promising target for MPNST treatment.

Objectives: To investigate the incidence and treatment strategies for bilateral upper tract urothelial carcinoma (UTUC) and to compare the characteristic and oncologic outcomes of bilateral UTUC with those of unilateral tumors., Methods and Materials: The study included 892 consecutive patients with UTUC. Bilateral UTUC was defined as synchronous bilateral carcinoma on preoperative imaging before confirmation by pathology or positive urine cytology result plus direct visualization. Radical nephroureterectomy (RNU) or nephron-sparing surgery (NSS) or both were carried out., Results: A total of 39 patients (4.37%) suffered from bilateral disease. Discordant histological grade of bilateral tumor was found in 39.3% cases. Bilateral tumors were associated with female sex (P<0.001), preoperative renal insufficiency (P<0.001), previous or concomitant bladder tumors (P = 0.013), lower tumor stages (P = 0.020), papillary architecture (P = 0.001), and smaller-sized tumors (P = 0.020). Patients with worse renal function (P<0.001) or large-sized tumors (P = 0.039) tended to be treated with bilateral RNU. Most patients (67.6%) were treated with unilateral RNU plus unilateral NSS, with NSS being performed on tumors that only extended to the ureter (P = 0.003) and had a smaller size (P = 0.005). The median follow-up duration was 56 months. The 5-year cancer-specific survival and bladder recurrence-free survival rates were 81.2% and 64.5%, respectively, similar to those of unilateral tumors. Male sex (hazard ratio = 11.535) and higher tumor stage (hazard ratio = 3.386) were independent worse prognostic factors., Conclusions: The prevalence of bilateral UTUC is rare. Female patients, patients with renal insufficiency, and those with bladder tumor tended to suffer from bilateral disease and were less likely to present with worse pathological outcomes in the Chinese population. The tumor characteristics and renal function were informative in treatment selection. The oncologic outcomes were similar to those in unilateral UTUC, and male sex and a higher tumor stage were poor prognostic factors for these patients., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The quality factor and mode volume of a nanocavity play pivotal roles in realizing the strong coupling interaction between the nanocavity mode and a quantum dot. We present an extremely simple method to obtain the mode volume and investigate the effect of the slab thickness on the quality factor and mode volume of photonic crystal slab nanocavities. We reveal that the mode volume is approximatively proportional to the slab thickness. As compared with the previous structure finely optimized by introducing displacement of the air holes, via tuning the slab thickness, the quality factor can be enhanced by about 22%, and the ratio between the coupling coefficient and the nanocavity decay rate can be enhanced by about 13%. This can remarkably enhance the capability of the photonic crystal slab nanocavity for realizing the strong coupling interaction. The slab thickness tuning approach is feasible and significant for the experimental fabrication of the solid-state nanocavities.

The diffraction spectra of Imaginary-Part Photonic Crystal (IPPC) slabs are analyzed by using Scattering-Matrix Method. By investigating the thickness dependence of the diffraction, we find the remarkable red shift of central wavelength of diffraction spectrum, which obviously distinguishes from the phenomenon of spectral hole. We observe that diffraction efficiency can be enhanced more than twentyfold by optimizing the geometry parameters. These imply that the diffraction spectra of the IPPC slab can be controlled at will and used to guide the design to achieve useful nanoscale devices.

Objective: To investigate the biomechanical characteristics of self-developed distraction reduction fixation system (DRFS) and to evaluate its clinical effect on thoracolumbar vertebrate fracture., Methods: Twelve fresh porcine spines were prepared for the biomechanical test. The stiffness of each intact specimen were recorded on forward bending (20 degrees), backward bending (10 degrees), lateral bending (30 degrees) and axial rotation (20 degrees), and then specimens of fracture dislocation were made by cuneiform osteotomy of L3 vertebral body and excision of posterior facet joints. Finally, DRFS internal fixation was performed on each specimen. The stiffness of specimens in fracture dislocation and after DRFS fixation were measured during the same movements mentioned above, respectively. The clinical effect of DRFS on thoracolumbar vertebrate fracture in 31 patients (aged 17-46 years with an average of 32.1) from April 1998 to October 2002 was summarized. Fracture types were classified according to Denis classification: 2 patients suffered simple compressed fracture, 16 burst fracture, and 13 fracture dislocation, including 2 cases of T11, 11 cases of T12, 14 cases of L1 and 4 cases of L2. Frankel and X-ray examination were adopted to assess the results., Results: The stiffness during forward bending, backward bending, lateral bending and axial rotation in the fracture-dislocation state was markedly lower than that of the corresponding movements of the intact porcine spines (P < 0.05). After DRFS, the stiffness during various movements increased to the level that significantly higher than that in the fracture-dislocation state (P < 0.05), and the stiffness during backward bending was of significant difference (P < 0.05), but without significant difference during the rest three movements (P > 0.05) when compared to that in intact spines. Regarding clinical observation, the operation time was 2.2-4.1 hours (2.7 hours on average) and blood loss was 250-600 mL (450 mL on average). The patients were followed up for 5-20 months (10.2 months on average). The healing time for fracture was 5-1 months (8 months on average). The mean anterior and posterior heights of the injured vertebrate recovered from 46.2% +/- 7.5% and 76.4% +/- 2.4% preoperatively to 89.8% +/- 4.6% and 94.1% +/- 1.5% postoperatively (P < 0.05).The median point height also raised from 60.8% +/- 6.4% to 90.7% +/- 2.9% (P < 0.05). The Cobb's angle decreased from (26.3 +/- 5.9)degrees to (5.2 +/- 1.8)degrees (P < 0.05), and all the slipped vertebrates were well repositioned. Spine function was assessed by Frankel classification as follows: 2 of 5 Class A preoperatively improved to Class B postoperatively, and the other 3 remained unchanged; 4 of 6 from B to C, and the other 2 to D; 6 of 13 from C to D, and the other 7 to E; and 7 from D to E., Conclusion: DRFS is capable of providing sufficient stability, meeting the requirement of the spine physical activity without any obvious side effect. DRFS, as a handy, safe and effective technique in clinical practice, is featured by satisfying functions of distraction, reposition and fixation.