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We have independent developed ZY6400/25/53 two-leg high cutting hydraulic shield supports firstly, which width was 1.5 m could adapt to much complicated geological conditions, reduced the hydraulic support and accessories costs, and solved the problems of supports’ stability efficiently. Industrial tests showed that the supports application were successful and effective. We realize the high efficient production, the average yield reach to the level of 10000 t/d, if mine system have working conditions, the coalface have the ability produce 5Mt coal annually. This hydraulic support greatly improve the coal resources mining rate, broaden the application range of the high cutting fully mechanized mining technology in China, and led the upgrade of mechanized equipment.

Based on the achieved engineering practice results of deep roadway drivage in Xinwen Mining Area, aimed at drivage problem of deep cross-level coal-rock, EBZ-135 fully-excavating machine had been used to replace traditional roadway blasting drivage, corresponding key technology of fast supporting for deep large sections of coal-rock roadway in high stress had been proposed, and latter mating transport system transformation of fully-mechanized fast drivage technology had been cooperated, which formed a suit of fully-mechanized fast drivage technology for deep large sections of coal-rock roadway in high stress. The application results show that the fully-mechanized fast drivage technology can markedly enhance the whole shaping quality of roadway, improve drivage efficiency and cycling footage immensely, reduce roadway drivage cost, and the good result of average month footage at 300 m and maximum month footage at 360 m have been achieved finally.

Under the condition of large inclined angle, the stability control of hydraulic support was always the challenge for the fully-mechanized mining in large inclined coal seams. Based on the specific geological conditions of 509 coalface with large inclined and high mining in Gaozhuang mine, the model of hydraulic support had been drawn by using SolidWorks software, and the inclination mechanical model of hydraulic support had been established to analyze its inclination stability along coalface. The calculation result shows that when the maximum inclination angle is 31° and the underhand angle is 10°, the minimum support resistance needed to keep the hydraulic support not dumping is 283.59 kN. Meanwhile, the critical support resistance required for the hydraulic support not to dump in inclination direction increases approximately linearly along with the increase of coalface mining height; under the same mining height condition, the critical support resistance increases along with the increase of the inclined angle. Therefore, the selection of the mining height and inclined angle of the coal seam must be considered at the beginning of the hydraulic support design.

Based on the different failure mechanism for shallow and deep rock mass, combined with the test result of ground stress and difficulties of blasting rock in Xinwen mining area, used mines rock mass mechanics and modern blasting theory and actively carried out technical reform, the new forming control technology of directional fracture blasting and control technology of multi-directional fusion blasting and efficient blasting technology of compound cut had been adopted, which produced a set of new efficient blasting rock technology for large section rock roadway drivage in deep shaft with complicated conditions. The engineering practice application results showed that the new efficient blasting rock technology could decrease the numbers of shot holes and explosive material consumption, enhance drivage efficiency and circulation footage, ameliorate integral forming quality of roadway and realize maximum month drilling footage at 146 m, the research achievements can provide reference for deep roadway drivage construction in other mining areas with similar conditions.

Objective The aim of this study was to evaluate the clinical characteristics and survival outcomes of patients with primary mediastinal germ cell tumor (PMGCT) by identifying the prognostic factors and efficacies of different treatment modalities. Methods Fifty-five patients with PMGCT who were treated consecutively at Cancer Center, Sun Yat-sen University, Guangzhou, from 1988 to 2010 were evaluated retrospectively. Results Fifty-two men and 3 women with a median age of 25 years were identified, of whom 17 (30.9%) had pure seminomatous, 38 (69.1%) had nonseminomatous histology, 27 (49.1%) had tumor located at mediastinum, 20 (36.4%) had lung metastases and/or effusions, and 8 (14.5%) had distant metastases. Three treatments surgery, chemotherapy, and radiotherapy were performed in 11 (20%) patients, two treatments chemotherapy plus surgery or radiotherapy were performed in 25 (45.6%), and single treatment surgery or chemotherapy was performed in 17 (30.9%). The other two patients (3.6%) received no treatment. After a median follow-up time of 31.4 months, the 5-year survival rate was 52%. The median overall survival time was 87.9 months. Patients who received two treatments had the longest survival time of 118.3 months, P = 0.000. Those who had pure seminoma histology, whose tumor confined to the mediastinum and who achieved complete or partial remission at initial evaluation, who had complete resection and radiotherapy were considered to have better prognosis according to univariate analysis. On multivariate analysis, extension and response rate at initial evaluation were independently predictive of survival. Conclusions Primary mediastinal germ cell tumor is rare with a dominant frequency in young male patients. Chemotherapy combined with local therapy like surgery or radiotherapy is a reasonable treatment strategy recommended. Extension and initial remission rate are independent prognostic factors.

To avoid the optional and uncertainty when judge self-organization clustering results, we have introduced the F-test method what have used in mathematical statistics. The method calculat and compares inner-class distance and inter-class distance respectively what from various clustering schemes, and then get the best clustering scheme through the F-test analysis. The experiment results show that the method is athematically proved rigorously, program operation is stable and reliable, and with larger value both in theoretical research and engineering application.

Modeled nonlinearity, time-varying, dynamic coupling finite element model of scraper conveyor according to its actual working condition in the mining, studied the transmission mechanism of bulk material power and its parameters test methods，constructed the shape function of scraper conveyor circuitry, realized the computer automatic modeling, by the example carried on digital simulation of all of working condition such as starting, freely stoppage, abnormal load, chains blocked, the difference of chain’s pitch and the chain wheel polygon effect, and so on.

The aim of this article is to deal with the difficulties of the private cars' parking. Through broad and deep research, this paper puts forward the design idea of combining the community landscape with the parking space, then the concept of landscape garage is introduced, and then multiple solutions are discussed to the private cars parking in communities by the method of brain storming. The "shell" project is developed in detail----the structure, shape, effect pictures are finished precisely. This design integrates landscape with garage and greatly improves space utilization, at the same time eases the parking difficulties.

The incidence of gastric cancer in young has increased steadily in the last decades. Little is known about the clinicopathologic features and prognostic factors of young adult gastric cancer patients. The clinicopathological characteristics of 294 young adult gastric cancer patients between 20 and 50 years old were reviewed retrospectively from hospital records in Sun Yat-Sen University Cancer Center between 1996 and 2006. They were compared with 706 elder patients 51 years of age or over. A steady increasing in the proportion of female in the gastric carcinoma patients as the age decreasing was found. The distinguishing histological features of young adult patients were higher percentage of poorly differentiated grade and distant metastasis. The distribution of tumor-nodes-metastasis (TNM) stage was similar between these two groups. The 5-year disease-specific survival rate in the young adult group was significantly higher than in the elderly group. More patients receiving adjuvant chemotherapy were found in the young adult group. Multivariable analysis demonstrated that TNM stage and presence of angiolymphatic invasion were the independent negative predictors of survival for young patients with gastric cancer. Gastric cancer in young patients differs from that in elderly patients including a lack of male predilection, more aggressive histologic features, and better survival rate.

Gastric cancer patients with negative nodes were considered to have better outcomes, however, some of them still suffered from disease recurrences or distant metastases after radical resection. A total of 1,020 gastric carcinoma patients receiving treatment in our center between 2003 and 2008 were selected for the analysis. All patients received gastrectomy and D2 lymphadenectomy. Survival analysis was performed with Cox regression model. The final study includes 222 patients. The overall 5-year disease-specific survival rate was 73.0%. Factors bearing significant association with lower survival on univariate analysis included the age of 58 years old or more (P = 0.021), tumor size longer than 4 cm (P < 0.001), presence of angiolymphatic invasion (P = 0.006), proximal site (P = 0.030), serosal invasion (T3+T4, P = 0.003), and higher TNM stage (P < 0.001). Only three factors including serosal invasion, tumor size at least 4.0 cm, and presence of angiolymphatic invasion remained independent negative predictors of survival in multivariable analysis. These parameters can be employed to select node-negative gastric cancer patients for an adjuvant setting and close follow-up scheduling.

Antibiotic-resistant bacteria (ARB) have been surveyed widely in water bodies, but few studies have determined the diversity of ARB in sediment, which is the most taxon-abundant habitat in aquatic environments. We isolated 56 extended-spectrum β-lactamase (ESBL)-producing bacteria from a single sediment sample taken from an urban river in China. All strains were confirmed for ESBL-producing capability by both the clavulanic acid combination disc method and MIC determination. Of the isolated strains, 39 were classified as Enterobacteriaceae (consisting of the genera Escherichia , Klebsiella , Serratia , and Aeromonas ) by 16S rRNA gene sequencing and biochemical analysis. The present study identifies, for the first time, ESBL-producing strains from the families Brucellaceae and Moraxellaceae . The bla CTX-M gene was the most dominant of the ESBL genes (45 strains), while the bla TEM gene was the second-most dominant (22 strains). A total of five types of bla CTX-M fragments were identified, with both known and novel sequences. A library of bla CTX-M cloned from the sediment DNA showed an even higher diversity of bla CTX-M sequences. The discovery of highly diverse ESBL-producing bacteria and ESBL genes, particularly bla CTX , in urban river sediment raises alarms for potential dissemination of ARB in communities through river environments.

2593Background: APG-1387 is a bivalent small molecule Smac mimetic that antagonizes the IAPs. Preclinical studies have shown its dose- and schedule-dependent, strong antitumor activities in multipl...

In exploiting shallow coal resources in western China, conservation of water resources is often subjugated to considerations of safety and production in coal mines. In order to maintain a sustainable development in the Shenfu-Dongsheng coalfield, we propose a technology of constructing groundwater reservoirs in goafs in shallow coalfields to protect fragile ecological environments. Given the premise of safe production, we selected an appropriate goaf as the site for constructing a groundwater reservoir and used a mine water recharge technique in combination with other related techniques for effective water conservation. Then filtering and purification techniques were used to purify the mine water given the physical and chemical properties of mine water and its filling material, thereby greatly reducing suspended matter, calcium and other harmful ions in the water. With the potential of widely application, the research result has been successfully applied in the Daliuta coal mine, to great economic and ecological effect. Therefore, this achievement provides a new way for mine water conservation in shallow coal resources in western China.

In this paper, we report a novel method for accurately measuring the photo-induced birefringence of germanosilicate fibers by using an all fiber Mach-Zehnder interferometer. The results indicate that the photo-induced normalized birefringence of C598-302(s) germanosilicate fiber can attain 10−5 and is multi-decaying-exponentially proportional to the UV exposure.

The effects of linear and quadratic strain on the reflective spectrum of FBG and the transmission spectrum of LPFG have been numerically investigated based on the coupled -mode equations. The results show that for the FBG or LPFG undergoing only linear strain, the reflection or transmission spectrum is symmetrical about its central wavelength, the dependence relationships of the central wavelength shift, full-width-at-half-maximum, peak intensity upon the strain gradient have been obtained.

To solve the problem of water loss during mining of shallow, buried coal seams, we have first analyzed the mechanism and suitability of solid-liquid coupling, i.e., we used the FLUID-MECHANICS system of 3-Dimensional Distinct Element Code (3DEC) in simulating dynamic water crannies in overlying strata, under mining conditions of a large longwall coalface. Next the dynamic initiation of a water cranny, its propagation and close phases were studied with 3DEC, along with the overlying strata breakage and recombination as the mining space of the shallow, buried coal seam increased. Combined with the change in the stress and displacement fields, the distribution features of the mining cranny were systematically studied. The effect of regularities and their effective measures of local filling and mine slicing technology in controlling mine crannies were investigated and the potential danger areas of water loss identified. Our results can be applied to decrease water loss during the exploitation of shallow, buried coal seams with a thin bedrock. The results also prove that 3DEC is a credible numerical analytical method to predict initiations of dynamic water crannies, their propagation, their closure phases and other concomitant hazards.

The room and pillar method is usually used to extract coal from shallowly buried seams with thin bedrock. This results in a very low production efficiency and in a low degree of extraction. In recent years short-wall continuous mechanical mining has been extensively used in many situations except shallowly buried coal seams with thin bedrock. The principles governing movement of the overlying strata above the 2-2 coal seam were deduced from in-situ experience, laboratory data, calculations and computer simulations. The thicknesses of the bedrock in the Shendong Coal Field where the coal is shallowly buried are classified into 5 types: 35 m, which was done using fuzzy clustering results. A series of reasonable, relative parameters in each category have been calculated and analyzed. One proposed way to perform short-wall continuous mechanical mining in shallowly buried coal seams is given. This is significant for coal mines with similar geological conditions.

Summary Background and objective: 5-fluorouracil (5-FU) is still a widely used anticancer drug. More than 85% of the 5-FU administered is catabolized by dihydropyrimidine dehydrogenase (DPD) in the liver. However, mutations in the DPD gene have been found to be associated with low DPD activity causing severe complications. The purpose of this study was to determine the mutation frequency of four exons in Chinese cancer patients and the relationship between genotype and DPD activity. Methods: Samples from 142 cancer patients were investigated in this study. The DPD activity was determined by reversed-phase HPLC. Exons 2, 13, 14 and 18 were amplified by polymerase chain reaction (PCR), sequenced and analysed from both sense and antisense directions. Nonparametric one-sample Kolmogorov–Smirnov test was used for distribution analysis; two independent samples t-test and one-way anova was performed for two groups and three groups analyses, respectively. Results and discussion: Plasma-DPD activities in the 142 cancer patients followed a Gaussian distribution. The mean plasma-DPD activity in women was lower than that in men (P = 0·006). Four mutations, 85T>C(DPYD*9A), 1627A>G(DPYD*5), 1896T>C and 2194G>A(DPYD*6), were found in the 142 cancer patients. The following mutations reported by others were not detected: 61C>T, 62G>A, 74A>G, 1601G>A(DPYD*4), 1679T>G(DPYD*13), 1714C>G, 1897delC(DPYD*3) and IVS 14 + 1G>A. No significant correlation was found between three mutations [85T>C(DPYD*9A), 1627A>G (DPYD*5) and 1896T>C], and DPD activity was found. Conclusion: No clear correlation between the mutations studied and DPD activity could be established in this study. However, larger-scale prospective studies are needed to better assess the reported genotype–phenotype correlations.

One of the main advantages of gene therapy over traditional therapy is the potential to target the expression of therapeutic genes in desired cells or tissues. To achieve targeted gene expression, we developed a novel heat-inducible gene expression system in which thermal energy generated by Mn-Zn ferrite magnetic nanoparticles (MZF-NPs) under an alternating magnetic field (AMF) was used to activate gene expression. MZF-NPs, obtained by co-precipitation method, were firstly surface modified with cation poly(ethylenimine) (PEI). Then thermodynamic test of various doses of MZF-NPs was preformed in vivo and in vitro. PEI-MZF-NPs showed good DNA binding ability and high transfection efficiency. In AMF, they could rise to a steady temperature. To analyze the heat-induced gene expression under an AMF, we combined P1730OR vector transfection with hyperthermia produced by irradiation of MZF-NPs. By using LacZ gene as a reporter gene and Hsp70 as a promoter, it was demonstrated that expression of a heterogeneous gene could be elevated to 10 to 500-fold over background by moderate hyperthermia (added 12.24 or 25.81 mg MZF-NPs to growth medium) in tissue cultured cells. When injected with 2.6 or 4.6 mg MZF-NPs, the temperature of tumor-bearing nude mice could rise to 39.5 or 42.8 degrees C, respectively, and the beta-gal concentration could increase up to 3.8 or 8.1 mU/mg proteins accordingly 1 day after hyperthermia treatment. Our results therefore supported hyperthermia produced by irradiation of MZF-NPs under an AMF as a feasible approach for targeted heat-induced gene expression. This novel system made use of the relative low Curie point of MZF-NPs to control the in vivo hyperthermia temperature and therefore acquired safe and effective heat-inducible transgene expression.

The aim of this study was to study in vitro and in vivo the killing effect and the bystander effect of herpes simplex virus-thymidine kinase gene/ganciclovir (HSV-TK/GCV) suicide gene system on the gastric cancer cell line, SGC-7901.GINaTK retroviral vector containing the HSV-TK gene was transduced into the PA317 packaging cell by lipofectin. The gastric cancer cell line, SGC-7901, was infected by a high-titer viral supernatant. SGC-7901/TK cells and SGC-7901 cells were used in the in vitro and in vivo studies. In the in vitro study, sensitivity of the SGC-7901/TK cells to GCV and the bystander effect were observated by a mononuclear cell direct cytotoxicity assay test. In the in vivo study, SGC-7901/TK cells and SGC-7901 cells were injected subcutaneously into the flanks of BALB/C nude mice, GCV was administrated intraperitoneally, a reverse transcriptase polymerase chain reaction was applied to detect the expression of the HSV-TK gene. A statistical analysis of the data was performed by using the analysis of variance.The SGC-7901 cells transferred with the GINaTK gene displayed a higher antitumor effect than the parent cells. In the in vitro study, when the ratio of SGC-7901/TK cells reached 10%, the tumor cell-killing proportion was 53%. In the in vivo study, all BALB/C nude mice developed tumors in 7 days after tumor cells were implanted, the ratio of tumors formation is 100%. GCV could suppress tumor formation of the SGC-7901/TK cells. After the BALB/C nude mice treated with GCV, compared with the control tumors the median tumor volume of the mice implanted with SGC-7901/TK cells and BALB/C nude mice with cells mixed was, respectively, decreased to 52.8% and 69.4%.The test showed that the HSV-TK gene can be transducted into the gastric cancer cell line, SGC-7901, under the mediation of a retrovirus and be stably expressed, and that the HSV-TK/GCV suicide gene therapy system could improve antitumoral efficiency. The bystander effect could be observated in the HSV-TK/GCV system both in vitro and in vivo.

Malignant tumors are the most serious threat to human health. Much research has focused on revealing the characteristics of this disease and developing methods of treatment. Because tumor cells are more sensitive to heat than normal cells, thermotherapy for the treatment of tumors has attracted much attention. In this paper, we presented functional Mn-Zn ferrite nanoparticles with the molecular composition of Mn0.4Zn0.6Fe2O4 as the magnetic response material for the thermotherapy. The suggested Mn-Zn ferrite nanoparticles were with a self-regulation temperature of 43 degrees C which was ideal for tumor thermotherapy. The biocompatibility and anti-tumor effect of this material were well investigated. It was found that the Mn0.4Zn0.6Fe2O4 nanoparticles have no hemolysis activity, no genotoxic effects and cytotoxicity. Its Median Lethal Dose (LD50) arrived at 6.026 g/kg and it did not induce any abnormal clinical signs in laboratory animals. Moreover, the suggested nanoparticles can increase the inhibitory ratio of weight and volume of tumors, cause tumor tissues necrosis and show the therapeutic effect on the xenograft live cancers in vivo. Based on these results, we could envision the valuable application of the Mn0.4Zn0.6Fe2O4 nanoparticles for the practical thermotherapy.

To investigate the prevalence of small intestinal bacterial overgrowth (SIBO) in patients with colorectal cancer (CRC) after surgical treatment and observe whether gastrointestinal symptoms may improve with rifaximin, 43 postoperative CRC patients (CRC group) and 30 healthy individuals (normal group) were subjected to the glucose hydrogen breath test (GHBT). All the patients were asked to evaluate the gastrointestinal symptoms using the visual analogue scale (VAS). SIBO-positive patients were administered rifaximin for 10 days on the basis of the original treatment. After the treatment, the patients were asked to undergo GHBT and re-evaluate the gastrointestinal symptoms score (GISS). The results demonstrated that 18 of the 43 postoperative patients with CRC were SIBO-positive (41.86%), which was significantly higher compared with the incidence in normal controls (6.67%) (P

The elevation of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) has been demonstrated to predict worse prognosis in various malignancies; however, their prognostic value in esophageal squamous cell carcinoma has not been well studied. We conducted a retrospective study of 906 patients with esophageal squamous cell carcinoma to explore their prognostic value for overall survival. The optimal cutoff points for ALP and LDH were determined. We analyzed the association between the levels of ALP and LDH and clinicopathological characteristics. Their prognostic value for overall survival was explored by univariate and multivariate analysis. We also proposed the ALP and LDH classification and examined its prognostic value in the general population and subgroups. The optimal cutoff points of ALP and LDH to predict overall survival were 90.7 and 361.5 U/L respectively. Higher levels of ALP and LDH were both associated with more advanced TNM stage (P = 0.003 and 0.002, respectively) and more distant metastasis (P = 0.001 and P 0.001, respectively). Both ALP (≤90.7/90.7 U/L) and LDH (≤361.5/361.5 U/L) were independent prognostic factors for overall survival in esophageal squamous cell carcinoma (P = 0.004 and P 0.001 by multivariate analysis). The ALP and LDH classification categorized patients into three subgroups with distinct prognosis (P 0.001 by multivariate analysis) and identified a small group of patients who had extremely poor overall survival with a median of 4.2 months. In conclusion, ALP and LDH were both independent prognostic factors for overall survival. A combination of the two indexes might contribute to further identification of survival differences in esophageal squamous cell carcinoma.

To study the influence of nodal liquefaction portion in the measurement of the ADC value of metastatic lymph nodes in patients with oral squamous cell carcinoma (OSCC) on DW-MRI images.According to the postoperative histopathological examination results, the DW-MRI data of 25 OSCC patients was analyzed. The ADC values of both solid portions of metastatic lymph nodes and the whole metastatic lymph nodes with internal liquefaction were selected and measured. Further comparison between the 2 groups was processed for 2 independent samples t test with SPSS 17.0 software package.Eleven patients out of all cases were diagnosed with cervical lymph node metastasis, and 15 metastatic lymph nodes were detected, among which 8 metastatic lymph nodes had obvious internal liquefaction. The average ADC values of solid portions of metastatic lymph nodes (group SMLN) and the whole metastatic lymph nodes with internal liquefaction (LMLN group) ADC were (872.1 ± 22.65) × 10⁻⁶ mm²/s (n=15) and (1073 ± 16.99) × 10⁻⁶ mm²/s (n=8), respectively. Two independent samples t test showed statistically significant difference of ADC values between group SMLN and group LMLN (P0.05).The internal liquefaction in OSCC metastatic lymph nodes can lead to an increased average ADC value. If the measurement of OSCC metastatic lymph nodes includes obvious liquefaction portions, it may reduce the diagnostic accuracy of DW-MRI for discrimination of lymph node metastasis.

After the approval of bevacizumab for the first-line treatment of metastatic colorectal cancer (mCRC) in China, published information was still limited. This observational cohort study enrolled 175 mCRC patients who initiated bevacizumab-containing first-line chemotherapies at Sun Yet-sen University Cancer Center. Backbone chemotherapies included FOLFIRI (45.6 %), FOLFOX (34.9 %), and XELOX (19.5 %). Effectiveness data, safety profiles, and treatment patterns were collected and compared between oxaliplatin- and irinotecan-based groups. The median treatment durations of bevacizumab in first-line and total were equivalent between oxaliplatin- and irinotecan-based group (5.0 vs. 4.8 and 6.0 vs. 5.9 months, respectively). Median progression-free survival (PFS) was 10.6 months, and median overall survival (OS) was 24.2 months in entire population. No significant difference was found between irinotecan- and oxaliplatin-based groups in PFS (10.8 vs. 10.1 months, p = 0.21) or in OS (27.5 vs. 23.7 months, p = 0.68). Overall response rate in entire population was 38.3 %, and the disease control rate was 86.3 %. Bevacizumab-associated serious adverse events included hypertension (4.2 %), bleeding (3.6 %), proteinuria (3.0 %), venous thromboembolism (0.6 %), and wound-healing complications (0.6 %). Curative-intent surgery after conversion chemotherapy was carried out in 23 patients (13.7 %). Multivariate analyses showed that maintenance therapy (p = 0.001), resection of metastatic sites (p = 0.002), and disease-free interval (p = 0.003) were independent prognostic factors for OS survival. In spite of small discrepancies in treatment patterns, irinotecan- and oxaliplatin-based chemotherapeutic regimens are equally compatible partners for bevacizumab in first-line Chinese mCRC treatment.

// Dong-liang Chen 1, 2 * , Dong-sheng Zhang 1, 2 * , Yun-xin Lu 1, 2 , Le-zong Chen 1, 2 , Zhao-lei Zeng 1, 3 , Ming-ming He 1, 2 , Feng-hua Wang 1, 2 , Yu-hong Li 1, 2 , Hui-zhong Zhang 1, 4 , Helene Pelicano 5 , Wei Zhang 6 , Rui-hua Xu 1, 2 1 State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China 2 Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China 3 Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China 4 Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China 5 Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA 6 Department of Pathology, Unit 85, Center for RNAi and Non-Coding RNA, University of Texas MD Anderson Cancer Center, Houston, TX, USA * These authors have contributed equally to this work Correspondence to: Rui-hua Xu, e-mail: xurh@sysucc.org.cn Keywords: microRNA, microRNA-217, EZH2, gastric cancer, metastasis Received: January 9, 2015 Accepted: February 25, 2015 Published: March 26, 2015 ABSTRACT microRNA-217 (miR-217) is frequently dysregulated in cancer. Here, we report that miR-217 levels were lower in tumor tissue compared with the adjacent normal tissue. Low levels of miR-217 were associated with aggressive tumor phenotypes and poor overall survival in gastric cancer patients. The ectopic expression of miR-217 inhibited cell proliferation, migration and invasion in vitro and tumor growth and metastasis in vivo , whereas knockdown of endogenous miR-217 increased cell proliferation and invasion. Further experiments revealed that Polycomb group protein enhancer of zeste homolog 2 (EZH2) was a direct target of miR-217 in gastric cancer cells. Knockdown of EZH2 mimicked the tumor-suppressive effects of miR-217 in gastric cancer cells, whereas the reintroduction of EZH2 abolished its effects. Taken together, these results demonstrated that miR-217 may be used as a prognostic marker, and the newly identified miR-217-EZH2 axis may be a potential target in the development of therapeutic strategies for gastric cancer patients.

TRIZ theory has been widely applied to the technical innovation. However it still lacks of efficient conflict-solving tools in the field of management innovation. In the study, we overview the use of tool in TRIZ for solving the technical and management innovation problem, such as the 40 Inventive Principles and 39 Technical Parameters that have been commonly applied. Our overview found that the 40 Inventive Principles can be used for the conflict-solving of management innovation, while the 39 Technical Parameters should be revised before its application. The Enterprise Environmental Parameters are necessary to solve the Management Conflict Matrix. The ideality of the innovation should be measured in the process to get the optimal solution.

AIM: To explore the association between AT-rich interactive domain 1A (ARID1A) protein loss by immunohistochemistry and both clinicopathologic characteristics and prognosis in patients with colorectal cancer. METHODS: We retrospectively collected clinicopathologic data and archived paraffin-embedded primary colorectal cancer samples from 209 patients, including 111 patients with colon cancer and 98 patients with rectal cancer. The tumor stage ranged from stage I to stage IV according to the 7th edition of the American Joint Committee on Cancer tumor-node-metastasis (TNM) staging system. All patients underwent resection of primary colorectal tumors. The expression of ARID1A protein in primary colorectal cancer tissues was examined by immunohistochemical staining. The clinicopathologic association and survival relevance of ARID1A protein loss in colorectal cancer were analyzed. RESULTS: ARID1A loss by immunohistochemistry was not rare in primary colorectal cancer tumors (25.8%). There were 7.4%, 24.1%, 22.2% and 46.3% of patients with ARID1A loss staged at TNM stage I, II, III and IV, respectively, compared with 20.0%, 22.6%, 27.7% and 29.7% of patients without ARID1A loss staged at TNM stage I, II, III and IV, respectively. In patients with ARID1A loss, the distant metastasis rate was 46.3%. However, only 29.7% of patients without ARID1A loss were found to have distant metastasis. In terms of pathologic differentiation, there were 25.9%, 66.7% and 7.4% with poorly, moderately and well differentiated tumors in patients with ARID1A loss, and 14.2%, 72.3% and 13.5% with poorly, moderately and well differentiated tumors in patients without ARID1A loss, respectively. ARID1A loss was associated with late TNM stage (P = 0.020), distant metastasis (P = 0.026), and poor pathological classification (P = 0.035). However, patients with positive ARID1A had worse overall survival compared to those with negative ARID1A in stage IV colorectal cancer (HR = 2.49, 95%CI: 1.13-5.51). CONCLUSION: ARID1A protein loss is associated with clinicopathologic characteristics in colorectal cancer patients and with survival in stage IV patients.

Inhibitors of angiogenesis and tumor metastasis are increasingly emerging as promising agents for cancer therapy. Here, we report λ-carrageenan oligosaccharides (λ-COs), highly-sulfated oligosaccharides acting as a basic fibroblast growth factor (bFGF) antagonist and heparanase inhibitor. λ-COs with degree of polymerization (DP) from 2 to 8 degraded by λ-carrageenase were separated and purified. The structures were identified by mass spectrometry. The activities of λ-COs are closely related with DP. λ-COs showed no cytotoxicity, but inactivated bFGF-induced cell proliferation; among them, λ-carraheptaose showed highest capability. Only λ-carraheptaose can effectively bind to bFGF. Binding kinetics showed that λ-carraheptaose and suramin had different binding modes, i.e., suramin displayed a fast association and fast dissociation, but λ-carraheptaose exhibited a slow association and slow dissociation. In addition, λ-COs showed the highest heparanase inhibitory ability and abolished the endothelial cell invasion. Thus, λ-COs may provide a tool to develop of new carbohydrate-based therapeutics against cancer and angiogenesis.

Less-teeth gear is increasingly promoted and applied because of the big single-stage transmission ratio, light weight, compact structure. The selection of gear parameters has been the key and difficult point of the design of less-teeth gear. At present design method involved in less-teeth gear design is rarely existed. According to the relationship between the characteristics and parameters of the less-teeth gear, using MATLAB for the optimization choice of the less-teeth gear, reasonable selection of the spiral angle and modification coefficient is realized, which can provide clues to further research of the less-teeth gear.

Prostatic utricles revealed by the presentation of haematuria are very rare. Only limited experience with laparoscopic surgery of prostatic utricle has been reported to date. Herein we report a 20-year-old male with frequently terminal haematuria and oligozoospermia who underwent successful laparoscopic excision of a large prostatic utricle. Haematuria disappeared and semen quality improved during 1-year follow-up.

128 Background: Advanced gastric cancer (AGC) is a major problem particularly in Asian countries. The treatment options are limited after standard first line chemotherapy. This phase I/II study aimed to evaluate the tolerability, pharmacokinetics and preliminary efficacy of fruquintinib, a selective oral VEGFR inhibitor, combined with paclitaxel as second-line therapy in Chinese patients with AGC. Methods: This open arm phase I/II trial (NCT02415023) consisted of dose finding and dose expansion stages. In the dose finding stage, 3 dose levels of fruquintinib (2, 3, 4 mg; once daily for 3 weeks) were evaluated in combination with standard 80 mg/m2 paclitaxel (once weekly on Days 1, 8 and 15) in a 28-day cycle until the maximum tolerated dose or recommended phase II dose (RP2D) was reached. Additional patients were enrolled at the RP2D to further assess the efficacy, safety and pharmacokinetic profile. Results: As of Sept. 10, 2016, a total of 32 patients were enrolled including 15 during dose escalation. The RP2D regimen was determined to be fruquintinib 4mg daily combined with paclitaxel 80mg/m2 weekly for 3 weeks followed by 1 week off in a 4 week cycle. Two patients at 4mg experienced dose-limiting toxicity, both with febrile neutropenia. The grade 3 or 4 treatment emergent adverse events were neutropenia (40.6%), leukopenia (28.1%), decreased hemoglobin (6.25%), hand-foot skin reaction (6.25%), neurophlegmon (6.25%), and hypertension (6.25%), more frequent in the 4mg cohort. At steady state, Fruquintinib AUC (AUCss) increased dose-proportionally and within the historic range as a single agent, while paclitaxel exposure, at the RP2D regimen, increased by approximately 30% compared to the AUC prior to fruqintinib dosing. Twenty-eight of 32 patients were evaluable for response, and of these, 10 patients had partial response (Objective Response Rate = 35.7%), 9 patients experienced stable disease for at least 8 weeks (Disease Control Rate = 67.9%). At RP2D, ≥ 16w-PFS = 50% and ≥ 7m-OS = 50%. Conclusions: Combination of fruquintinb and paclitaxel appeared to be generally well-tolerated with promising tumor response. Further evaluation in a controlled phase II study is warranted. Clinical trial information: NCT02415023.

The aim of our study is firstly to evaluate the prevalence and prognostic value of nutrition risk in gastric cancer patients and secondly to explore whether the nutrition support can prolong the survival of advanced gastric cancer patients. It contained two study periods. In the first period, we prospectively evaluated the nutritional risk of gastric adenocarcinoma patients from 2009 to 2011 using the method of European Nutritional Risk Screening (NRS) 2002. The Kaplan-Meier method and log-rank test were used to evaluate the prognostic value of high nutrition risk. The second period was between 2012 and 2013. We prospectively gave the nutrition support to stage IV gastric cancer patients whose NRS is ≥3. There were 830 patients in the first period, 50.7 % patients with a NRS ≥ 3. Patients with NRS ≥ 3 presented a significantly higher percentage of stage IV diseases, elevated values of C-reactive protein, and hypoproteinemia. The median survival was significantly higher in NRS

To investigate the expression of p53 and Beclin1 in salivary pleomorphic adenoma (PA) and its clinical significance.The expression of p53 and Beclin1 were assessed by immunohistochemistry in 108 cases of PA and 20 cases of carcinoma in pleomorphic adenoma(CIPA). The results were used to analyze the relationship between gene expressions and the development of PA as well as the clinical pathological features. Statistic analysis was conducted with SPSS 20.0 software package.The positive expressions of p53 in PA samples (9%) were significantly lower than that in CIPA(14%) (P0.001). The positive expressions of autophagy-related gene Beclin1 in PA samples(91%) were significantly higher than that CIPA (11%) (P0.001). The expression levels of these genes were not associated with gender, age, clinical course, tumor size, and location of PA(P0.05). There was a negative correlation between p53 and Beclin1 expression in PA (r=-0.330,P0.05).The expression levels of Beclin1 and p53 protein are closely related to the development of PA. Reduced autophagy and enhanced anti apoptosis coexist in the process of tumor formation. Thus, raising the autophagy ability may become another alternative choice for cancer therapy.

Several large studies have reported an extremely low incidence of MET gene amplification (GA) in patients with radically resected gastric cancer. This study was conducted to evaluate the prevalence and prognostic role of MET in patients with recurrent=metastatic gastric cancer who received chemotherapy.MET GA and protein expression of recurrent=metastatic gastric cancer samples were evaluated by fluorescence in situ hybridization and immunohistochemistry (IHC), respectively.This retrospective study included 232 patients with recurrent=metastatic gastric cancer. MET GA and strong protein expression(IHC31) were observed in 8.3% (19 of 230 samples) and 9.6% (22 of 229 samples) of samples, respectively. A significant correlation was observed between MET GA and protein expression (r = 0.378; P.001). MET GA was correlated with poor performance status(P.001) and poorly differentiated tumors (P=.0015). Both MET GA and IHC 31 expression were associated with a substantially shorter median overall survival (OS) and progression-free survival (PFS). The median OS and PFS for patients with MET GA versus those without MET GA were 5.7 months versus 15.5 months (P.001) and 3.6 months versus 6.9 months (P.001), respectively. The median OS and PFS for patients with MET IHC 31 expression versus IHC 0 to 21 expression were 6.3 months versus 15.1 months(P.001) and 3.6 months versus 7.0 months (P.001), respectively.In patients with recurrent=metastatic gastric cancer,MET amplification and strong protein expression are not rare and appear to be significantly associated with unfavorable clinical outcomes.

Burkitt's lymphoma (BL) is a highly aggressive type of non-Hodgkin's lymphoma, with marked rates of proliferation and metabolism. The expression levels of the translocated cellular Myc (c-Myc) oncogene and Epstein-Barr virus infection have an oncogenic role in facilitating tumor progression and maintaining a malignant phenotype in BL Raji cells. The present study identified that more reactive oxygen species (ROS) were produced in Raji cells compared with other types of malignant B cells. Cells exhibiting higher ROS levels suggested facilitation of the induction of cell death by ROS-induction compounds. In the present study, apogossypolone (ApoG2) was observed to induce marked accumulation in the levels of ROS in the Raji cells, which damaged the cells and suppressed cell proliferation. Within 12 h following ApoG2 treatment, the Raji cells were prominently arrested in the G1 phase of the cell cycle. Immunoblotting analysis indicated that the chromodomain-helicase-DNA-binding protein 1, checkpoint kinase 1 and c-Myc proteins were significantly downregulated at 3, 6 and 12 h, respectively, following treatment. Following treatment with ApoG2 for 48 h, ApoG2 induced significant apoptosis in the Raji cells. This findings, together with our previous studies, which demonstrated ApoG2 as a potent inhibitor of anti-apoptotic B cell lymphoma 2 proteins, indicated that the ROS stimulatory effect of ApoG2 increased the antitumor activity of ApoG2.

This work aims to study the preparation and characterization of curcumin and gold nanorods-loaded albumin nanoparticles and investigate its treatment for MCF-7 human breast cancer cells in vitro. Gold nanorods (GNRs) were prepared by seedless method. While the curcumin and gold nanorods-loaded albumin nanoparticles (Cur/GNRs-BSA-NPs) were prepared by desolvation-crosslinking method, with the characteristics detected by dynamic light scattering (DLS), transmission electron microscope (TEM) and ultraviolet photometer. The results indicated that the GNRs and Cur/GNRs-BSA-NPs were prepared successfully. The prepared GNRs, which are rectangular and round-ended, have uniform sizes and good dispersion. The Cur/GNRs-BSA nanoparticles were spherical with exact average diameter of 190nm. The Cur/GNRs-BSA-NPs did not show cytotoxicity in vitro after tested by the CCK-8 assay. Thermodynamic test was employed to observe the temperature change of various doses of Cur/GNRs-BSA-NPs at the near-infrared (NIR) light exposure with the wavelength of 808 nm and the output power of 2.5 W. It was found that the Cur/GNRs-BSA-NPs induced significant temperature elevation and curcumin release upon irradiation with NIR light. The anti-tumor effect on MCF-7 human cancer cells treated with Cur/GNRs-BSA-NPs in vitro was evaluated by CCK-8 assay. The experimental results revealed that Cur/GNRs-BSA-NPs could significantly inhibit the proliferation of MCF-7 cells with combined treatment. Moreover, the coating of albumin could help reduce toxicity of GNRs and improve the bioavailability of the insoluble curcumin. The Cur/GNRs-BSA-NPs developed in this work present a new potential method combining both traditional Chinese and western medical treatment for human breast cancer.

The distribution of the polymorphic alleles of the genes coding for glutathione S-transferases (GSTs) M1 and T1 was compared with the results of cytological grading of exfoliated urothelial cells (Pap test) in a non-diseased high-risk group of workers formerly exposed to benzidine in the Shanghai dyestuff industry (n = 317). All subjects were genotyped for GSTT1 and M1 gene polymorphism by allele-specific PCR. Individuals were stratified according to their job and duration of exposure. A subgroup of 78 individuals with cytological gradings of grade III or higher in the Pap test showed a significant under-representation of the combination of GSTT1 0/0 and M1 0/0 genotypes compared with 238 subjects with a cytological classification lower than grade III (OR 0.55, 95% CI 0.31-0.98. P=0.04). These results suggest that neither the GSTM1 0/0 or GSTT1 0/ 0 genotype alone nor their combination had a clear association with cytopathological changes in exfoliated urothelial cells from individuals previously exposed to benzidine in Shanghai. This contradicts the results of studies indicating that the GSTM1 0/0 genotype is associated with an increased risk for bladder cancer in the general population, mostly outside China.

The present observational cohort study was designed to elucidate the efficacy and safety profile of bevacizumab or cetuximab with chemotherapy as the first-line treatment in Chinese patients with metastatic colorectal cancer (mCRC). Clinical data were collected from a single-center registry

The purpose of this study was to identify microRNAs (miRNAs) involved in the pathology of colorectal cancer (CRC) liver metastasis and investigate their underlying mechanisms. A total of 39 miRNAs were identified to be differentially expressed between 16 primary CRC tissues with liver metastases and 16 CRC tissues without liver metastases from 32 patients by Affymetric miRNA microarrays. A panel of eight miRNAs were confirmed to be significantly and differentially expressed between CRC tissues with and without liver metastases through quantitative reverse-transcription polymerase chain reaction (RT-PCR) analysis in the 32 patients. In a validated cohort of 99 CRC patients (44 with and 55 without liver metastases), only miR-214 was validated to be significantly down-regulated in CRC with liver metastases, which was associated with an unfavorable prognosis. Ectopic expression of miR-214 suppressed proliferation, migration, and invasion in vitro, tumor growth and liver metastasis in an in vivo xenograft mouse model, whereas miR-214 knockdown promoted proliferation, migration, and invasion in CRC cell lines. Further studies indicated that fibroblast growth factor receptor 1 (FGFR1) was a potential target of miR-214. Restoring miR-214 expression in CRC cells decreased endogenous FGFR1 messenger RNA (mRNA) and protein levels. FGFR1 knockdown mimicked the tumor suppressive effect of miR-214 on CRC cells, while reintroduction of FGFR1 abolished the tumor suppressive effect of miR-214 on CRC cells. Moreover, miR-214 expression levels were inversely correlated with FGFR1 in CRC patients. Conclusion: Down-regulation of miR-214 expression was correlated with increased FGFR1 expression levels, which may contribute to increased CRC liver metastasis. miR-214 may serve as a potential marker to predict survival, and the miR-214-FGFR1 axis may be a therapeutic target in CRC patients. (Hepatology 2014;60:598–609)

Background Metabolic syndrome and/or its components have been demonstrated to be risk factors for several cancers. They are also found to influence survival in breast, colon and prostate cancer, but the prognostic value of metabolic syndrome in gastric cancer has not been investigated. Methods Clinical data and pre-treatment information of metabolic syndrome of 587 patients diagnosed with early stage gastric cancer were retrospectively collected. The associations of metabolic syndrome and/or its components with clinical characteristics and overall survival in early stage gastric cancer were analyzed. Results Metabolic syndrome was identified to be associated with a higher tumor cell differentiation (P = 0.036). Metabolic syndrome was also demonstrated to be a significant and independent predictor for better survival in patients aged >50 years old (P = 0.009 in multivariate analysis) or patients with proximal gastric cancer (P = 0.047 in multivariate analysis). No association was found between single metabolic syndrome component and overall survival in early stage gastric cancer. In addition, patients with hypertension might have a trend of better survival through a good control of blood pressure (P = 0.052 in univariate analysis). Conclusions Metabolic syndrome was associated with a better tumor cell differentiation in patients with early stage gastric cancer. Moreover, metabolic syndrome was a significant and independent predictor for better survival in patients with old age or proximal tumors.

Background It has been proved that hepatitis B virus (HBV) infection alters the metastatic pattern and affects survival in colorectal cancer (CRC) and hepatocellular carcinoma (HCC), while the influence of HBV infection on metastatic pattern and survival in patients with pancreatic cancer (PC) has not been investigated yet. Methods We conducted an investigation to evaluate the impact of HBV infection on metastatic pattern and overall survival in PC. We collected the data of 460 PC patients treated in our hospital from 1999 to 2010. Serum HBV markers were tested with enzyme-linked immunosorbent assay. The impact of HBV infection on metastatic pattern and overall survival was analyzed. Results We found that the incidence of synchronous liver metastasis was significantly higher in patients with HBsAg positive than those with HBsAg negative (46.0% vs 32.0%, P < 0.05), and higher in chronic HBV infection (CHB) group than both non HBV infection and resolved HBV infection group (61.1% vs 33.9%, P < 0.05, and 61.1% vs 28.7%, P < 0.05, respectively). What’s more, Kaplan-Meier analysis showed that CHB, resolved HBV infection and non HBV infection group had significant longer overall survival (OS) compared with inactive HBsAg carriers (IC) group (P=0.037, P=0.009, and P=0.019 respectively). But, in the multivariate analysis, only the CHB and non HBV infection group had significant better overall survival compared with IC group (P=0.010 and P=0.018 respectively). Conclusions Our study found that HBV infection increased synchronous liver metastasis rate, and HBV infection status was an independent prognostic factor in PC patients.

AIM: To investigate adjuvant chemotherapy, p53 and carcinoembryonic antigen (CEA) expression and prognosis after D2 gastrectomy for stage II/III gastric adenocarcinoma. METHODS: A total of 286 patients with stage II or III gastric adenocarcinoma who underwent D2 radical gastrectomy between May 2007 and December 2010 were enrolled into this study. One hundred and sixty-nine of these patients received surgery plus adjuvant chemotherapy, and 117 patients received surgery alone. Tumor expression of p53 and CEA proteins in all patients was evaluated immunohistochemically and correlated with clinicopathological parameters. The Kaplan-Meier curves for overall survival (OS) and disease-free survival (DFS) with log-rank testing were used to compare the survival difference. A Cox proportional hazard regression model was used for multivariate analysis. RESULTS: Patients with adjuvant chemotherapy had a significantly better median OS (50.87 mo vs 30.73 mo, P = 0.000) and median DFS (36.30 mo vs 25.60 mo, P = 0.001) than patients with surgery alone in the entire cohort. Consistent results with the entire cohort were found in stage II (P = 0.006 and P = 0.047), stage III (P = 0.005 and P = 0.030), and stage IIIB/IIIC patients (P = 0.000 and P = 0.001). The median OS and DFS advantages were confirmed by multivariate analysis (P = 0.000 and P = 0.008) and maintained when the analyses were restricted to fluoropyrimidine monotherapy (P = 0.003 and P = 0.001) and fluoropyrimidine plus platinum regimen (P = 0.001 and P = 0.007), however, not the fluoropyrimidine plus taxane (P = 0.198 and P = 0.777) or platinum plus taxane (P = 0.666 and P = 0.687) regimens. Median OS and median DFS did not differ significantly between the patients with p53(+) and p53(-) tumors (P = 0.608 and P = 0.064), or between patients with CEA(+) and CEA(-) tumors (P = 0.052 and P = 0.989), which were maintained when the analyses were restricted to surgery alone (p53: P = 0.864 and P = 0.431; CEA: P = 0.142 and P = 0.948), adjuvant chemotherapy (p53: P = 0.802 and P = 0.091; CEA: P = 0.223 and P = 0.946) and even different chemotherapy regimens (P > 0.05). CONCLUSION: Patients after D2 gastrectomy for stage II/III gastric adenocarcinoma had significantly better survival after fluoropyrimidine monotherapy and fluoropyrimidine plus platinum. p53 and CEA were not prognostic.

Background Primary small cell carcinoma of the esophagus (SCCE) is a highly aggressive disease characterized by early dissemination and poor prognosis. Because of the rarity of this disease, few previous studies have investigated the biomarkers associated with its prognosis. Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) is a stem cell marker and a member of the canonical Wnt-signaling cascade. However, the clinical role of Lgr5 in SCCE remains unknown. Methods Tissue sections were obtained from 44 patients diagnosed with SCCE and expression of Lgr5 was examined by immunohistochemistry. The correlations between Lgr5 expression, and clinical parameters and prognostic significance were evaluated. Results Lgr5 was expressed in SCCE cancer tissues. High Lgr5 expression was significantly correlated with lymph node metastasis (p = 0.003), late stage (p = 0.003) and unfavorable response to chemotherapy (p = 0.013) according to RECIST 1.0 criteria. Patients with higher Lgr5 expression levels had shorter overall survival times than those with lower expression levels. Conclusions These results demonstrated that overexpression of Lgr5 was significantly correlated with lymph node metastasis, tumor stage, and response to chemotherapy. Furthermore, high levels of Lgr5 expression appeared to be associated with poorer survival in patients with SCCE.

The monoclonal antibody trastuzumab has brought survival benefit to patients with advanced gastric cancer (AGC) that have human epidermal growth factor receptor 2 (HER2) over expression or amplification. This study was designed to compare the clinical outcomes of HER2-negative and HER2-positive AGC patients with or without trastuzumab treatment. There were three groups of patients enrolled for analysis. Group A was 51 HER2-positive AGC patients treated with trastuzumab and chemotherapy; group B was a matched control group of 47 HER2-positive patients who received chemotherapy only; group C was a matched group of 251 HER2-negative patients who received chemotherapy. All the patients were enrolled at Sun Yat-sen University Cancer Center or Zhongshan Hospital, Fudan University between January 2010 and December 2012. The primary endpoint was overall survival (OS). The Kaplan-Meier method and log-rank test were used for survival analysis. The median duration of follow-up was 13.5 months (range 5-18.6 months). The median OS of these three groups of patients was 14.8 months, 11.3 months and 14.4 months respectively (p0.001). The survival difference between group A and B was significant, p0.001. Similarly, there was significant difference between group B and C, p0.001. Moreover the survival between group A and C was comparable, p = 0.281. The median progression-free survival for these three groups was 7.4, 6.0 and 7.2 months. Multivariate analysis confirmed that trastuzumab treatment was an independent prognostic factor in group A and B patients (p = 0.017). HER2 positive was an independent adverse prognostic factor in group B and C patients (p = 0.013).

Background Paxillin (PXN) has been found to be aberrantly regulated in various malignancies and involved in tumor growth and invasion. The clinicopathological and prognostic significance of PXN in gastric cancer is still unclear. Methods The expression of PXN was determined in paired gastric cancer tissues and adjacent normal tissues by Western blotting and real-time PCR. Immunohistochemistry was performed to detect the expression of PXN in 239 gastric cancer patients. Statistical analysis was applied to investigate the correlation between PXN expression and clinicopathological characteristics and prognosis in patients. Additionally, the effects of PXN on gastric cancer cell proliferation and migration were also evaluated. Results PXN was up-regulated in gastric cancer tissues and cell lines as compared with adjacent normal tissues and normal gastric epithelial cell line GES-1. Overexpression of PXN was correlated with distant metastasis (P = 0.001) and advanced tumor stage (P = 0.021) in gastric cancer patients. Patients with high PXN expression tended to have poor prognosis compared with patients with low PXN expression (P P = 0.020). Moreover, ectopic expression of PXN promotes cell proliferation and migration in AGS cells whereas knockdown of PXN inhibits cell proliferation and migration in SGC7901 cells. Conclusions PXN plays an important role in tumor progression and may be used as a potential prognostic indicator in gastric cancer.

Background The cell division cycle 20 homolog (CDC20) is an essential cofactor of the anaphase-promoting complex (APC/C). CDC20 overexpression has been detected in many types of human cancers; however, its clinical role in colorectal cancer remains unknown. Methods Western blotting and immunohistochemistry were used to compare CDC20 expression in adjacent non-cancerous, cancerous and liver metastatic tissues as well as in colon cancer cell lines and normal colon epithelial cell lines. Additionally, the correlation of CDC20 expression with patient clinical parameters and its diagnostic value were statistically analyzed. Results CDC20 was overexpressed in colon cancer cell lines/primary cancer tissues compared with normal colon epithelial cell lines/adjacent noncancerous tissue samples. Interestingly, CDC20 expression was further increased in metastatic liver tissues. CDC20 protein expression was significantly correlated with clinical stage (P = 0.008), N classification (P = 0.020), M classification (P = 0.013) and pathologic differentiation (P = 0.008). Patients with higher CDC20 expression had a shorter overall survival than those with lower CDC20 expression. Univariate and multivariate analyses indicated that CDC20 expression was an independent prognostic factor (P < 0.001). Conclusion CDC20 may serve as a potential prognostic biomarker of human colorectal cancer.

The primary objective of this study was to evaluate the dose-limiting toxicities (DLTs) and identify the maximum-tolerated dose (MTD) and recommended dose of nab-paclitaxel plus gemcitabine as a first-line treatment in Chinese patients with advanced pancreatic ductal adenocarcinoma (PDA).Patients with previously untreated advanced PDA were treated with nab-paclitaxel followed by gemcitabine (1,000 mg/m(2)) administered intravenously for 30 min on days 1 and 8 and repeated every 21 days.Patients received nab-paclitaxel at the following dose levels: 80 mg/m(2) (n = 3), 100 mg/m(2) (n = 6), and 120 mg/m(2) (n = 12). The DLTs evaluated were elevated alanine aminotransferase and febrile neutropenia. However, there had no two out of three to six patients experienced DLTs, the MTD was not met. A total of 93 cycles were administered. The most common grade 3/4 toxicities were neutropenia (9.52 %), thrombocytopenia (4.76 %), and sensory neuropathy (4.76 %). For 12 patients receiving 120 mg/m(2), the overall response rate and disease control rate were 41.67 and 83.33 %, respectively, and the median progression-free survival and overall survival were 5.23 and 12.17 months, respectively.Treatment with albumin-bound nab-paclitaxel (120 mg/m(2)) plus gemcitabine has a favorable safety profile with an encouraging antitumor effect in Chinese patients.

The deregulation of paxillin (PXN) has been involved in the progression and metastasis of different malignancies including colorectal cancer (CRC). miR-137 is frequently suppressed in CRC. PXN is predicted to be a direct target of miR-137 in CRC cells. On this basis, we hypothesized that overexpression of PXN induced by suppression of miR-137 may promote tumor progression and metastasis and predicts poor prognosis. We detected the expression of PXN and miR-137 in clinical tumor tissues by immunohistochemical analysis and real-time PCR, positive PXN staining was observed in 198 of the 247 (80.1%) cases, whereas no or weak PXN staining was observed in the adjacent non-cancerous area. Higher level of PXN messenger RNA (mRNA) and lower level of miR-137 was observed in cancer tissues than adjacent non-cancerous tissues. High expression of PXN and low expression of miR-137 was associated with aggressive tumor phenotype and adverse prognosis. Moreover, the expression of PXN was negatively correlated with miR-137 expression. A dual-luciferase reporter gene assay validated that PXN was a direct target of miR-137. The use of miR-137 mimics or inhibitor could decrease or increase PXN mRNA and protein levels in CRC cell lines. Knockdown of PXN or ectopic expression of miR-137 could markedly inhibit cell proliferation, migration and invasion in vitro and repress tumor growth and metastasis in vivo. Taken together, these results demonstrated that overexpression of PXN induced by suppression of miR-137 promotes tumor progression and metastasis and could serve as an independent prognostic indicator in CRC patients.