A novel anti-lung cancer agent inhibits proliferation and epithelial-mesenchymal transition.

OBJECTIVE: To synthesize a novel chalcone-1,3,4-thiadiazole hybrid and investigate its anticancer effects against NCI-H460 cells. METHODS: (E)-3-(4-bromophenyl)-1-(4-hydroxyphenyl)prop-2-en-1-one, 1,3-dibromopropane and 1,3,4-thiadiazole-2-thiol were used as chemical materials to synthesize compound ZW97. The NCI-H460 lung cancer cell line was selected to explore the antitumor effects of compound ZW97 in vitro and in vivo. RESULTS: Compound ZW97 selectively inhibited cell proliferation against lung cancer cell lines NCI-H460, HCC-44 and NCI-H3122 with IC50 values of 0.15 µM, 2.06 µM and 1.17 µM, respectively. ZW97 suppressed migration and the epithelial-mesenchymal transition process in NCI-H460 cells in a concentration-dependent manner. Based on the kinase activity results and docking analysis, compound ZW97 is a novel tyrosine-protein kinase Met (c-Met kinase) inhibitor. It also inhibited NCI-H460 cell growth in xenograft models without obvious toxicity to normal tissues. CONCLUSIONS: Compound ZW97 is a potential c-Met inhibitor that might be a promising agent to treat lung cancer by inhibiting the epithelial-mesenchymal transition process.

A Novel Nanoprobe for Targeted Imaging and Photothermal/Photodynamic Therapy of Lung Cancer.

An effective accumulation of the photosensitive drugs in the target tissues is a vital prerequisite for obtaining the optimal photodynamic or photothermal treatment effects during the lung cancer treatment. In this study, porous Fe3O4 nanoparticles were used to efficiently load the near-infrared photosensitive drug indocyanine green (ICG) in the pores (denoted as Fe/ICG) by electrostatic adsorption. Subsequently, Fe/ICG was modified with hyaluronic acid (HA) to construct a novel target nanoprobe (denoted as Fe/ICG@HA). Fe/ICG@HA exhibited not only excellent ICG loading and stability but also a significant uptake by the lung cancer cells owing to the targeting characteristics. Meanwhile, the nanoprobe improved the efficiency of thermal conversion and generation of singlet oxygen, thereby resulting in an optimal photothermal/photodynamic therapy effect. Based on the in vivo experiments and T2-magnetic resonance (MR) imaging, the nanoprobe was confirmed to possess excellent tumor-targeting abilities. Furthermore, under 808 nm laser irradiation, a significant therapeutic effect was observed on the tumor growth in the animal models. The proposed treatment strategy may provide a functional pathway for the targeted combined photothermal/photodynamic lung cancer therapy.

Clinical Features and Survival Outcome of Early-Stage Primary Pulmonary MALT Lymphoma After Surgical Treatment.

Background: We aimed to study the clinical features and survival outcomes of patients with early-stage primary pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma who underwent surgery. Methods: This is a retrospective, single-center study including 32 patients with early-stage primary pulmonary MALT lymphoma. Univariate and multivariate Cox analyses were performed to select independent prognostic factors. The overall survival (OS) was analyzed by the Kaplan-Meier method and was compared with the log-rank test. Results: Among the 32 patients included, there were 16 men (50.0%) and 16 women (50.0%). The average age was 59.2 years old. Ten patients had non-specific clinical symptoms including cough, expectoration, and chest pain, and four patients had B symptoms. CT images are not specific and can be shown as peripheral, central, solid, and ground glass but more peripheral (93.8%) and solid (75.0%). In prognostic analysis, univariate analysis showed that tumor stage and size were associated with relapse-free survival (RFS) and OS [hazard ratio (HR) = 1.105, 95% CI: 1.021-1.197, P = 0.011; HR = 1.211, 95% CI: 1.158-1.968, P = 0.003, respectively]. It seems to indicate that higher stage and larger size indicate a worse prognosis, but we could not find statistically significant predictors in multivariate analysis. Sublobectomy was performed in 21 (65.6) cases, lobectomy was performed in the other 11 (34.4) cases, both of them can achieve good prognosis (5-year RFS and OS are both 100%), and there is no significant difference between them. Conclusions: The clinical manifestation of early-stage primary pulmonary MALT lymphoma is not significantly specific, and surgical resection is an effective treatment.

Effects of miR-132-3p on progress and epithelial mesenchymal transition of non-small cell lung cancer via regulating KLF7.

BACKGROUND: MicroRNAs (miRNAs) often appear as oncogenes or tumor suppressor genes. The aim of this research was to examine miR-132-3p and Kruppel-like factor 7 (KLF7) effects in the development of non-small cell lung cancer (NSCLC). METHODS: We used quantitative reverse transcription polymerase chain reaction (qRT-PCR) to determine miR-132-3p expression in tissue specimens and 6 cells (A549, H1650, H292, H1299, H1944, BEAS-2b). Luciferase report forecasted the targeting relationship between miR-132-3p and KLF7. The expression of KLF7 and interstitial protein was determined by western blot. Proliferation test and Transwell assay were adopted for examining cell development. The Cell Counting Kit-8 (CCK-8) colorimetric method was used to observe the effects of miR-132-3p and KLF7 on the proliferation, metastasis, and invasion of NSCLC tumor cells. In order to determine whether the metastasis of NSCLC tumor cells was epithelial-mesenchymal transition (EMT)-mediated, supplementary experiments with E-cadherin and vimentin were performed. RESULTS: An increased expression of miR-132-3p was detected in NSCLC. Its mimic promoted the proliferation of tumor cells. As an immediate site of miR-132-3p, KLF7 was reversely adjusted via miR-132-3p and restrained the development of tumor cells in NSCLC, the effects of which were attenuated via KLF7 over-expression. Besides, the presence of EMT-related diversions was confirmed in NSCLC. CONCLUSIONS: By targeting KLF7, miR-132-3p was capable of promoting the proceeding of NSCLC tumor cells. We discovered miR-132-3p/KLF7 route may exhibit curative target for NSCLC.

MiR-384 induces apoptosis and autophagy of non-small cell lung cancer cells through the negative regulation of Collagen α-1(X) chain gene.

The present study aims to investigate the mechanism of miR-384 in non-small cell lung cancer (NSCLC) cell apoptosis and autophagy by regulating Collagen α-1(X) chain (COL10A1). Bioinformatics methods were applied to evaluate potential miRNAs and genes that might correlate with NSCLC. Tumor tissues and adjacent tissues from 104 NSCLC patients were collected and human NSCLC A549 cell line was selected for subsequent experiments. A549 cells were treated with miR-384 mimic, miR-384 inhibitor, or knockdown of COL10A1. Quantitative real-time PCR (qRT-PCR) and Western blotting were utilized to detect the levels of miR-384, COL10A, Survivin, Bcl-2, Bax, Bcl-xl, Beclin 1, and LC3 in tissues and cells. A series of biological assays including MTT assay, Annexin V-FITC/PI (propidium iodide) staining, immunofluorescence, monodansylcadaverine (MDC) staining were conducted to investigate the effects of miR-384 and COL10A1 on NSCLC cells. Tumorigenicity assay for nude rats was applied. Results obtained from the present study indicated that miR-384 down-regulated COL10A1 by targetting it. Compared with adjacent tissues, miR-384 expression was obviously reduced while COL10A1 expression was significantly enhanced in NSCLC tissues (all P<0.05). Outcomes in vivo and in vitro suggested that cell proliferation and tumorigenicity were inhibited while cell apoptosis and autophagy were induced in NSCLC cells treated with up-regulation of miR-384 or silence of COL10A1. In miR-384 inhibitor group, cell proliferation was improved, while cell apoptosis was reduced and cell autophagy was decreased whereas tumorigenicity of cells was strengthened. Based on the findings of our study, it was established that miR-384 could down-regulate COL10A1 levels, subsequently inhibiting cell proliferation and promoting cell apoptosis and autophagy in NSCLC cells.

Delivery of CD151 by Ultrasound Microbubbles in Rabbit Myocardial Infarction.

OBJECTIVES: We aimed to evaluate whether ultrasound (US) and microbubble-mediated delivery of Cluster of Differentiation 151 (CD151) could enhance the therapeutic effects of CD151 on myocardial infarction (MI). METHODS: A rabbit model of MI was established by a modified Fujita method. Then, 50 MI rabbits were randomly divided into 5 groups, including G1 (CD151 plasmid and physiological saline in the presence of US); G2 (CD151 and Sonovue in the presence of US); G3 (CD151 and Sonovue in the absence of US); G4 (Sonovue in the absence of US), and a control group (physiological saline in the absence of US). After 14 days of treatment, the expression of CD151 was detected by Western blot. Besides, vessel density of peri-infarcted myocardium was measured by immunohistochemistry, and cardiac function was analyzed by echocardiography. RESULTS: The rabbit model of MI was established successfully. CD151 injection increased the expression of CD151 and microvessel density in the myocardium of MI rabbits. Heart function was significantly improved by CD151, which exhibited increased left ventricular ejection fraction, left ventricular fractional shortening and a reduced Tei index. Besides, US Sonovue significantly increased the expression efficiency of CD151. CONCLUSION: US microbubble was an effective vector for CD151 delivery. CD151 might be an effective therapeutic target for MI.

Influence of ischemia before vein grafting on early hyperplasia of the graft and the dynamic changes of the intima after grafting.

BACKGROUND: To investigate both the influence of ischemia before grafting on early hyperplasia of the vein grafts, and the dynamic changes of the intima after grafting in a rabbit model of vein graft disease. METHODS: We performed paired vein graft experiments under different ischemic conditions (15 vs. 60 min; 15 vs. 90 min) in the neck of the rabbits and compared the differences between the grafts. Clopidogrel, an anti-platelet agent, was administered before and after surgery. Twenty-eight days after the grafting procedure, the veins were evaluated microscopically. The dynamic changes of the intima after grafting were evaluated by scanning electron microscopy over time. RESULTS: The vein grafts subjected to 60- or 90-min ischemia exhibited no differences compared to those subjected to 15-min ischemia in terms of the mean thickness of the intimal, medial, and adventitial layers of the graft. Similarly, there was no difference in the Ki-67 labeling index (proliferation marker) between the vein grafts. Vein grafts with 15-min ischemia lost endothelial cells (ECs) but healed by 3 days post graft, whereas vein grafts with 90-min ischemia suffered serious EC loss, which was restored with new ECs during days 2 to 14 post graft. CONCLUSIONS: Ninety-minute ischemia before vein grafting can cause serious EC loss, but does not increase early intimal hyperplasia when clopidogrel is administered. Protecting the vein from ischemia and reperfusion injury preserves ECs.

In vivo evaluation of a novel dexamethasone-heparin-double-coated stent for inhibition of artery restenosis and thrombosis.

To evaluate the efficacy and safety of dexamethasone-heparin-double-coated stent (DHDCS) on inhibition of artery lumen reduction and neointimal hyperplasia in porcine model we carried out this study. Bare mental stents (BMS, n = 12), protein-coated stents (PCS, n = 12), heparin microballoon-coated stents (HMCS, n = 12), and DHDCS (n = 12), prepared by the spray drying method, were implanted into the selected internal iliac artery, external iliac artery, sacrococcygeal artery, and femoral artery of each of the selected pigs (n = 12), which were randomly divided into four groups on average. Thirty days and ninety days after the implantation, aorta angiography was performed on all the 12 mini-pigs to evaluate the artery lumen reduction. Subsequently, in order to analyze their histological appearance, the pigs were killed, and their arteries with the stents inside were taken out, embedded in plastic for hard histological section and hematoxylin-eosin (H.E.) staining, and examined by light microscopy and scanning electron microscopy (SEM). The artery lumen reduction and average neointimal hyperplasia in the group of DHDCS were significantly lesser than those in the other three groups of BMS, PCS, and HMCS. This study shows that DHDCS is capable of inhibiting the proliferation of intima and lumen area reduction of the target artery within stents, and effectively and safely reducing the incidence of regional thrombosis and restenosis for a short term.

In vivo study on the histocompatibility and degradation behavior of biodegradable poly(trimethylene carbonate-co-D,L-lactide).

The aim of this study was to explore the in vivo behavior and histocompatibility of poly(trimethylene carbonate-co-D,L-lactide) (PDLLA/TMC) and its feasibility of manufacturing cardiovascular stents. Copolymers with 50/50 molar ratio were synthesized by ring-opening polymerization with TMC and D, L-LA, or TMC and L-LA. Poly(L-lactide) (PLLA) was synthesized as a control. The films of the three polymers were implanted into 144 Wistar rats. At different time points of implantation, polymer films were explanted for the evaluation of degradation characteristics and histocompatibility using size exclusion chromatography , nuclear magnetic resonance , environmental scanning electron microscope , and optical microscope. Results showed that there were differences in the percentage of mass loss, molecular weight, shape and appearance changes, and inflammation cell counts between different polymers. With the time extended, the film's superficial structure transformed variously, which was rather obvious in the polymer of PDLLA/TMC. In addition, there were relatively lower inflammation cell counts in the PDLLA/TMC and poly(trimethylene carbonate-co-L-lactide) (PLLA/TMC) groups at different time points in comparison with those in the PLLA group. The differences were of statistical significance (P< 0.05) in the group of PDLLA/TMC vs. PLLA, and the group of PLLA/TMC vs. PLLA, but not within the PDLLA/TMC and PLLA/TMC groups (P> 0.05). These results suggested that the polymer of PDLLA/TMC (50/50) with favorable degradation performance and histocompatibility is fully biodegradable and suitable for manufacturing implanted cardiovascular stents.

Off-pump occlusion of trans-thoracic minimal invasive surgery (OPOTTMIS) on simple congenital heart diseases (ASD, VSD and PDA) attached consecutive 210 cases report: a single institute experience.

OBJECTIVE: This paper intends to report our experiences by using an operation of off-pump occlusion of trans-thoracic minimal invasive surgery (OPOTTMIS) on the treatment of consecutive 210 patients with simple congenital heart diseases (CHD) including atrial septal defect (ASD), ventricular septal defect (VSD) and patent ductus arteriosus (PDA). METHODS: The retrospective clinical data of OPOTTMIS in our institute were collected and compared to other therapeutic measures adopted in the relevant literatures. After operation, all the patients received electrocardiography (ECG) and echocardiography (echo) once a month within the initial 3 months, and no less than once every 3 ~ 6 months later. RESULTS: The successful rate of the performed OPOTTMIS operation was 99.5%, the mortality and complication incidence within 72 hours were 0.5% and 4.8%, respectively. There were no major complications during peri-operation such as cardiac rupture, infective endocarditis, strokes, haemolysis and thrombosis. The post-operation follow-up outcomes by ECG and echo checks of 3 months to 5 years showed that there were no III° AVB, no obvious Occluder migration and device broken and no moderate cardiac valve regurgitation, except 1 VSD and 1 PDA with mild residual shunts, and 2 PDA with heart expansion after operation. However, all the patients' heart functions were in class I~II according to NYH standard. CONCLUSION: The OPOTTMIS is a safe, less complex, feasible and effective choice to selected simple CHD patients with some good advantages and favorable short-term efficacies.

Evaluation of a novel paclitaxel-eluting stent with a bioabsorbable polymeric surface coating in the porcine artery injury model.

PURPOSE: Drug-eluting stents (DES) are unique in allowing sustained release after a single short intervention. The challenge with DES still remaining is the optimal combination of a biocompatible drug-eluting matrix including an antiproliferative drug. We studied the role of a novel paclitaxel-eluting stent with a bioabsorbable polymer coating in preventing vascular restenosis in the porcine artery injury model. MATERIAL AND METHODS: Bare metal stents (BMS); polymer-coated-only stents (POLY); and polymer-based paclitaxel-eluting stents (PACL) were randomly implanted in pig femoral arteries. The dose density of paclitaxel was 1 microg/mm2 with in vitro studies demonstrating a gradual elution over a course of 6 month. RESULTS: After 1-, 3- and 6-month follow-up, respectively, the animals underwent angiographic restudy and were terminated for histomorphometrical and histopathological analyses. At 1 month, the PACL group had the lowest histological percent stenosis when compared to the BMS and POLY groups (20 +/- 4% vs 39 +/- 6% and 41 +/- 6%, respectively, P < 0.05). At 3 months, the PACL group still presents the lowest level of histological percent stenosis among the three groups (27 +/- 6% vs 50 +/- 10% and 46 +/- 5%, respectively, P < 0.01). Six months later, the PACL group showed a similar histological percent stenosis as the BMS and POLY groups (44 +/- 9% vs 56 +/- 11% and 53 +/- 9%, respectively, P = 0.145). CONCLUSIONS: This study shows favourable vascular compatibility and efficacy for a novel DES to inhibit in-stent neointima formation and preserve lumen area in the porcine artery model.

[Potassium channel blocker regulates the proliferation of prostatic epithelial cells in SD rats].

OBJECTIVE: To investigate the regulatory effect of potassium channel blocker (tetraethylammonium [TEA], aminopyridine [4-AP], glibenclamide [Glib]) on the proliferation of SD rat prostatic epithelial cells in vitro. METHODS: The primary culture was prepared by collagenase dissociation of minced prostatic tissues. Cells were cultured in serum-free prostate epithelial cell growth media and identified by immunocytochemical studies. TEA and 4-AP at the concentration of 1, 5 and 10 mmol/L and Glib at the concentration of 10, 50 and 100 mol/L were added, and after 24, 48 and 72 hours of culturing, a cell column diagram was drawn and the cell number counted. The post-passage cell growth was observed by MTT assay and Hoechst33258 nucleus staining. RESULTS: The cultured cells showed the typical morphological features of epithelia, with positive stain. MTT assay and Hoechst33258 staining showed that TEA, 4-AP and Glib at the increasing concentration effected different degrees of proliferation of prostatic epithelial cells after 24, 48 and 72 h (P < 0.01). CONCLUSION: The potassium channel blocker is a direct physiological regulator of the proliferation of SD rat prostatic epithelial cells.

[Epidemiological study of chronic prostatitis patients with depression symptoms].

OBJECTIVE: To study the depression symptoms in chronic prostatitis (CP) patients, and explore the correlation between depression symptoms and CP. METHODS: The Zung self-rating depression scale (SDS) , NIH-CPSI, IIEF-5, and a self-designed questionnaire were employed in 1500 cases of CP patients. RESULTS: A total of 1426 effective questionnaires were collected. The mean score of SDS was (44.24 +/- 10.20), significantly higher than that of the domestic norm (P = 0.000). With the score limitation set at > or = 53, 309 (21.7%) of the CP patients had symptoms of depression, of whom 176 (12.3%) were rated by SDS as in the mild, 114 (8.0%) in the moderate and 19 (1.3%) in the severe state of depression. The dominating symptoms as listed in SDS were exactly the stimulating and provoking factors of CP. The scores of SDS were significantly correlated with disease course, CPSI score, IIEF score and times and cost of treatment (P < 0.01), while no correlation was observed with age and WBC counts in EPS. CONCLUSION: CP patients mostly have depression problems, which are closely correlated with CP and contribute to the recurrence, refractoriness and discontinued outcome of the disease.

K channel expression in prostate epithelium and its implications in men with chronic prostatitis.

OBJECTIVE: To investigate the effect of the Kv1.3 K(+) channel on the pathogenesis of chronic prostatitis. MATERIALS AND METHODS: The expression of the Kv1.3 K(+) channel in prostatic epithelia was detected using streptavidin/peroxidase immunohistochemistry in tissue samples from 75 men with benign prostatic hyperplasia, including 42 with and 33 without chronic inflammation. All of the men were sampled in our hospital between January 2000 and December 2003. RESULTS: There was strong and moderate immunostaining in 14 of the prostatic epithelial specimens with inflammation and in 21 from patients without inflammation, compared to 28 and 12 with low staining, respectively (chi-squared, P < 0.05). CONCLUSIONS: The expression of the Kv1.3 K(+)channel was lower in prostatic epithelial cells from patients with chronic inflammation than from those without. Opening the Kv1.3 K(+) channel could promote the efflux of K(+) from the cells, causing an increase in [K(+)] in the prostate cavity. The increase in [K(+)] can then infiltrate the stroma through the epithelial gap, exciting the nerve fibres and causing pain and other clinical symptoms.

[Potassium ion channels and prostatic diseases].

Potassium ion channels are a complex of protein molded in the cell membrane lipids. Its expression is strong in normal prostatic epithelia and weak in different degrees in prostatic cancer epithelia, but not clearly known in chronic prostatitis epithelia. Drugs affecting potassium ion channels could provide a new direction and some new ideas for the treatment of prostatic diseases.