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Osteosarcoma, a highly aggressive malignant tumor of the bone, usually occurs in children and young adults. However, although the considerable achievement in the clinical treatment of osteosarcoma recent years, the overall survival of osteosarcoma patients has not been obviously improved. Cancer cells preferentially use glycolysis instead of oxidative phosphorylation to meet their increased energetic and biosynthetic demands, a phenomenon known as the Warburg effect. Glycolysis is a driving factor in multiple cancers and is emerging as a new cancer target treatment. In the present study, we established a model to screen for glycolysis-associated genes in osteosarcoma. This risk score of the model were correlated with clinical characteristics osteosarcoma patients. Besides, a functional assay identified that STC2 enhanced the glycolysis of osteosarcoma cells. Modulation of STC2 changes glucose consumption and lactate production as well as GLUT1 expression in osteosarcoma. Furthermore, we identified that change in the expression levels of STC2 affected the proliferation, invasion, and migration of osteosarcoma cells. Our findings showed STC2 as a new tumor-promoting factor of osteosarcoma cells through enhancing glycolysis.

The metabolic change of tumor cells is an extremely complicated process that involves the intersection and integration of various signal pathways. Compared with normal tissues, cancer cells show distinguished metabolic characteristics called metabolic reprogramming, which has been considered as a sign of cancer occurrence. With the deepening of tumor research in recent years, people gradually found that amino acid metabolism played crucial roles in cancer progression. Long non-coding RNAs (lncRNAs), which are implicated in many important biological processes, were firstly discovered dysregulating in cancer tissues and participating in extensive regulation of tumorigenesis. This review focuses on the reprogramming of amino acid metabolism in cancers and how lncRNAs participate in the regulatory network by interacting with other macromolecular substances. Understanding the functions of lncRNA in amino acid reprogramming in tumors might provide a new vision on the mechanisms of tumorigenesis and the development of new approaches for cancer therapy.

Background: Osteosarcoma (OS) is a tumor with a high malignancy level and a poor prognosis. First-line chemotherapy for OS has not been improved for many decades. Bromodomain and extra terminal domain (BET) and histone deacetylase (HDACs) regulate histone acetylation in tandem, and BET and HDACs have emerged as potential cancer therapeutic targets. Methods: Cell proliferation, migration, invasion, colony formation, and sphere-forming assay were performed with the two inhibitors alone or in combination to evaluate their suppressing effect on malignant properties of OS cells. The apoptosis and cells-cycle profile were measured by flow cytometry. The synergistic inhibitory effect of OTX015/WT-161 on tumor was also examined in a nude mouse xenograft model. Results: The combined therapy of OTX015/WT-161 synergistically inhibited the growth, migration, and invasion and induced apoptosis, resulted in the G1/S arrest of OS cells. Additionally, OTX015/WT-161 inhibits the self-renewal ability of OS stem cells (OSCs) in a synergistic manner. Further mechanistic exploration uncovered that the synergistic downregulation of β-catenin by OTX015-mediated suppression of FZD2 and WT-161-mediated upregulation of PTEN may be responsible for the synergistic effect. Finally, the result of an in vivo assay showed that tumor xenografts were significantly decreased after treatment with OTX015/WT-161 combination compared with OTX015 or WT-161 alone. Conclusion: Our findings in this study demonstrated that OTX015 and WT-161 had a synergistic anti-cancer efficacy against OS, and their combination might be a promising therapeutic strategy for OS.

Background: WT161, as a selective HDAC6 inhibitor, has been shown to play anti-tumor effects on several kinds of cancers. The aim of the present study is to explore the roles of WT161 in osteosarcoma and its underlying mechanisms. Methods: The anti-proliferative effect of WT161 on osteosarcoma cells was examined using MTT assay and colony formation assay. Cell apoptosis was analyzed using flow cytometer. The synergistic effect was evaluated by isobologram analysis using CompuSyn software. The osteosarcoma xenograft models were established to evaluate the anti-proliferative effect of WT161 in vivo. Results: WT161 suppressed the cell growth and induced apoptosis of osteosarcoma cells in a dose- and time-dependent manner. Mechanistically, we found that WT161 treatment obviously increased the protein level of PTEN and decreased the phosphorylation level of protein kinase-B (AKT). More importantly, WT161 showed synergistic inhibition with 5-FU on osteosarcoma cells in vitro and in vivo. Conclusions: These results indicate that WT161 inhibits the growth of osteosarcoma through PTEN and has a synergistic efficiency with 5-FU.

Background: WT161 as a new selective HDAC6 inhibitor has been shown to play anti-tumor effects on multiple myeloma and breast cancer. However, the role of WT161 in osteosarcoma remains unclear. The aim of this study is to explore the role of WT161 in osteosarcoma and its underlying mechanisms.Methods: The anti-proliferative effect of WT161 on osteosarcoma cells was examined using MTT assay and colony formation assay. Cell apoptosis was analyzed using flow cytometer. The synergistic effect was evaluated by isobologram analysis using CompuSyn software. The osteosarcoma xenograft models were esatablished to evaluate the anti-proliferative effect of WT161 in vivo.Results: WT161 suppressed the cell growth and induced apoptosis of osteosarcoma cells in a dose- and time-dependent manner. Mechanistically, we found that WT161 treatment obviously increased the protein expression level of PTEN and decreased the phosphorylation level of AKT. Notably, WT161 shows synergistically inhibitory effects on osteosarcoma cell combined with 5-FU. Animal experiment results show WT161 inhibits the growth of osteosarcoma tumor and further illustrates that WT161 and 5-FU have a synergistic efficiency in osteosarcoma.Conclusions: These results indicate that WT161 inhibiting the growth of osteosarcoma through PTEN and has a synergistic efficiency with 5-FU.

Background The current published prognosis models for brain metastases (BMs) from cancer have not addressed the issue of either newly diagnosed non–small-cell lung cancer (NSCLC) with BMs or the lung cancer genotype. We sought to build an adjusted prognosis analysis (APA) model, a new prognosis model specifically for NSCLC patients with BMs at the initial diagnosis using adjusted prognosis analysis (APA). Patients and Methods The model was derived using data from 1158 consecutive patients, with 837 in the derivation cohort and 321 in the validation cohort. The patients had initially received a diagnosis of BMs from NSCLC at Sun Yat-Sen University Cancer Center from 1994 to 2015. The prognostic factors analyzed included patient characteristics, disease characteristics, and treatments. The APA model was built according to the numerical score derived from the hazard ratio of each independent prognostic variable. The predictive accuracy of the APA model was determined using a concordance index and was compared with current prognosis models. The results were validated using bootstrap resampling and a validation cohort. Results We established 2 prognostic models (APA 1 and 2) for the whole group of patients and for those with known epidermal growth factor receptor (EGFR) genotype, respectively. Six factors were independently associated with survival time: Karnofsky performance status, age, smoking history (replaced by EGFR mutation in APA 2), local treatment of intracranial metastases, EGFR-tyrosine kinase inhibitor treatment, and chemotherapy. Patients in the derivation cohort were stratified into low- (score, 0-2), moderate- (score, 3-5), and high-risk (score 6-7) groups according to the median survival time (16.6, 10.3, and 5.2 months, respectively; P Conclusion Compared with recursive partition analysis and graded prognostic assessment, APA seems to be more suitable for initially diagnosed NSCLC with BMs.

In this paper, a bandgap voltage reference (BGR) with a low temperature coefficient, used for readout circuits of SPAD, has been designed and fabricated successfully in the standard MXIC 0.5µm 1P3M CMOS process. The area of the core circuit occupies 244×215µm2. The test results show that the designed bandgap reference could work normally under the power supply voltage of 2.8V to 8V with a line regulation (LNR) of 0.0096%. At room temperature (25°C), the stable reference output voltage is 1.168V. The reference voltage varies by only 1.8mV within the temperature range of 0~150°C, and leads to a temperature coefficient of 10.28ppm/°C. Under the power supply of 5V, the BGR chip exhibits a power supply rejection ratio (PSRR) of 76.4dB at 1KHz.

Thin-walled structures are of great importance in automotive crashworthiness design, because of their high crash energy absorption capability and their high potential for light weighting. To identify the best compromise between these two requirements, numerical optimization is needed. Size and shape optimization is relatively well explored while topology optimization for crash is still an open issue. Hence, this paper proposes an approach based on hybrid cellular automata (HCA) for crashworthiness topology optimization with a special focus on thin-walled structures. First approaches have been published, e.g. Duddeck et al. (Struct Multidiscip Optim 54(3):415---428, 2016), using a simple rule to define the target mass for the inner loop of the HCA. To improve the performance, a modified scheme is proposed here for the outer optimization loop, which is based on a bi-section search with limited length. In the inner loop, hybrid updating rules are used to redistribute the mass and a mass correction technique is proposed to make the real mass converge to the target mass strictly. The efficiency and correctness of the proposed method is compared with LS-OPT for axial crash case. Two different methods of defining the target mass in the outer loop are studied, the proposed bi-section search with limited length shows its advantage in two types of three-point bending crash optimization cases. Another advantage of this method is that it requires no significantly increasing number of evaluations when the number of design variables increases. This is demonstrated by applying this method to a crashworthiness optimization problem with 380 design variables.

Although topology optimization is well established in most engineering fields, it is still in its infancy concerning highly non-linear structural applications like vehicular crashworthiness. One of the approaches recently proposed and based on Hybrid Cellular Automata is modified here such that it can be applied for the first time to thin-walled structures. Classical methods based on voxel techniques, i.e., on solid three-dimensional volume elements, cannot derive structures made from thin metal sheets where the main energy absorption mode is related to plastic buckling, folding and failure. Because the main components of car structures are made from such thin-walled beams and panels, a special approach using SFE CONCEPT was developed, which is presented in this paper.

// Tao Qin 1,* , Yin-duo Zeng 1,2,* , Ge Qin 1,* , Fei Xu 1,* , Jia-bin Lu 1 , Wen-feng Fang 1 , Cong Xue 1 , Jian-hua Zhan 1 , Xin-ke Zhang 1 , Qiu-fan Zheng 1 , Rou-jun Peng 1 , Zhong-yu Yuan 1 , Li Zhang 1 and Shu-sen Wang 1 1 Sun Yat-sen University Cancer Center, The State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, P. R. China 2 Sun Yat-sen University Sun Yat-sen Memorial Hospital, Guangzhou, Guangdong, P. R. China * These authors have contributed equally to this work Correspondence to: Shu-sen Wang, email: // Li Zhang, email: // Zhong-yu Yuan, email: // Keywords : PD-L1, breast cancer, ER, PR, prognosis, nomogram Received : July 07, 2015 Accepted : August 22, 2015 Published : September 10, 2015 Abstract Background: To investigate the role of PD-L1 expression in tumor recurrence and metastasis in Chinese patients with breast cancer. Methods: Suitable tissue samples were available from 870 patients with breast cancer. Paraffin-embedded tumor sections were stained with PD-L1 antibody. The correlations between PD-L1 expression and clinical characteristics, ER/PR/HER2 status and survival parameters were analyzed. Kaplan-Meier and univariate Cox proportional hazards model analyses were used to compare the survival of patients with high PD-L1 expression and patients with no PD-L1 expression. Results: The median follow-up time was 98 months(range, 17–265 months).The positive rate of PD-L1 expression in breast cancer was 21.7% (189/870). PD-L1 high expression was inversely associated with larger tumor size, higher tumor grade, more positive lymph node number, as well as negative ER and PR status. PD-L1 expression was particularly higher in TNBC compared with non-TNBC, although no statistical significance was observed. Nomogram logistic regression results based on clinical and pathological features showed that the following factors were more likely associated with high PD-L1 expression: patient age younger than 35 years, larger tumor size, lymphovascular invasion and advanced stage. Our data indicated that patients with high PD-L1 expression had poor DFS, DMFS and overall survival compared with those with no PD-L1 expression. Univariate Cox proportional hazards model analysis showed that PD-L1 was an independent prognostic factor for tumor prognosis. Conclusions: PD-L1 expression is an important indicator of unfavorable prognosis in breast cancer patients.

Toxic epidermal necrolysis (TEN) is a rare acute life-threatening mucocutaneous disorder that is mostly drug-related (80%-95%). It is clinically characterized as a widespread sloughing of the skin and mucosa. AP regimen (pemetrexed plus cisplatin) has been the preferred first-line chemotherapy for metastatic non-squamous non-small cell lung cancer (NSCLC). Gefitinib, a small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has already been recommended as a first-line treatment in EGFR-mutant metastatic NSCLC. We report rare presentation of TEN involving adverse effects of AP and gefitinib combination treatment in a 42-year-old woman diagnosed with metastatic NSCLC harboring an EGFR mutation. On the 21st day after administration of the first cycle of AP regimen and the 8th day after the initiation of gefitinib treatment, she developed an acne-like rash, oral ulcer, and conjunctivitis, which later became blisters and ultimately denuded. The characteristic clinical courses were decisive for the diagnosis of TEN. Treatment with systemic steroids and immunoglobulin as well as supportive treatment led to an improvement of her general condition and a remarkable recovery.

Introduction The aim of the study was to analyze clinicopathologic characteristics and survival and to identify prognostic factors for Chinese patients with HER2-positive metastatic breast cancer. Material and methods A total of 243 patients with HER2-positive metastatic breast cancer, treated during the period 2002 to 2009, were followed up from initial disease diagnosis to death or date of last follow-up (December 2011). Cumulative survival curves were created using Kaplan-Meier analysis with the log-rank test. Prognostic factors were analyzed by univariate and multivariate Cox proportional hazards regression analysis. Results During follow-up, 205 patients died, with a median OS of 27 months (95% CI: 23.5, 30.5 months), and the 1-, 3-, and 5-year survival rates were 84.4%, 38.6%, and 18.1%, respectively. The median OS of HR+ patients was significantly higher than that of HR– patients (p < 0.001). Surgery (hazard ratio = 0.60, p = 0.002), endocrine therapy (hazard ratio = 0.53, p < 0.01), and anti-HER2 therapy (hazard ratio = 0.63, p = 0.003) were favorable independent prognostic factors for patients with HER2-positive metastatic breast cancer. Conclusions These results indicated that surgical intervention, endocrine therapy, and anti-HER2 therapy were good for these HER2 positive patients with metastatic breast cancer, but ECOG performance status < 1 and metastasis to brain were unfavorable independent prognostic factors. HR status was not an independent prognostic factor.

Crashworthiness design and optimization is of great importance in the automotive industry. However, due to the high computational cost and numerical noise, crashworthiness topology optimization is not studied so intensively. In this paper, a relatively new method, the Hybrid Cellular Automata for Thin-walled Structures (HCATWS) is used in its improved version. In particular, its applicability is extended from structures with an initially regular grid to structures with different size of cells (sets of a higher number of finite elements). The corresponding modifications of the algorithm are discussed here. This also affects the updating rules used in the improved version; hence, the theory is revised and modified where necessary. In the outer loop of the HCATWS, bi-section search within limited length is used to define the target mass. In the inner loop, HCATWS utilizes proportional updating to redistribute the mass for each cell. Then mass correction is conducted to make sure the real mass converges to the target mass. Here the different sizes of the cells need to be considered. As applications, one linear static case is studied to demonstrate efficiency of the approach. Then, additional crash cases using nonlinear dynamic FEM are considered. Finally, the potential of using this approach for identification of optimal cross-sections of structures originating from Additive Manufacturing (AM) is explored. Here, it is important that optimized topology results from HCATWS are more easily manufactured compared to those obtained by traditional element-based, i.e. voxel-based, topology optimization.

The fates of cadmium (Cd) and arsenic (As) in paddy fields are generally opposite; thus, the inconsistent transformation of Cd and As poses large challenges for their remediation. In this study, the impacts of zero valent iron (ZVI) and/or biochar amendments on Cd and As bioavailability were examined in pot trials with rice. Comparison with the untreated soil, both Cd and As accumulation in different rice tissues decreased significantly in the ZVI-biochar amendments and the Cd and As accumulation in rice decreased with increasing ZVI contents. In particular, the concentrations of Cd (0.15 ± 0.01 mg kg−1) and As (0.17 ± 0.01 mg kg−1) in rice grains were decreased by 93% and 61% relative to the untreated soil, respectively. A sequential extraction analysis indicated that with increasing Fe ratios in the ZVI-biochar mixtures, bioavailable Cd and As decreased, and the immobilized Cd and As increased. Furthermore, high levels of Fe, Cd, and As were detected in Fe plaque of the ZVI-biochar amendments in comparison with the single biochar or single ZVI amendments. The ZVI-biochar mixture may have a synergistic effect that simultaneously reduces Cd and As bioavailability by increasing the formation of amorphous Fe and Fe plaque for Cd and As immobilization. The single ZVI amendment significantly decreased As bioavailability, while the single biochar amendment significantly reduced the bioavailability of Cd compared with the combined amendments. Hence, using a ZVI-biochar mixture as a soil amendment could be a promising strategy for safely-utilizing Cd and As co-contaminated sites in the future.

This paper develops a novel approach for the lightweight design of a car body frame. In this approach, the cross-sectional dimensions of a car body frame are treated as design variables. First, sampling points are created based on Latin Hypercube Sampling (LHS), and then Design of Experiment (DOE) is conducted. After that, an analysis is done to obtain those design variables affect the results most. Finally, Sequential Quadratic Programming (SQP) is utilized to solve the optimization problem while the amount of design variables is reduced according to the former analysis. The advantage of this method is that it reduces the burden of optimization algorithms and offers a practical way for the lightweight design of a car body frame.

Due to its high packaging strain and shape memory effect, elastic memory composite (EMC) has considerable potential application in future deployable space structures. Buckling of the reinforcing fibers is the primary deformation mechanism of such a new class of functional materials to realize a higher folding strain than that of conventional fiber reinforced composites. In this paper, the orientation of buckling direction of the reinforcing fibers in EMC laminate will be theoretically analyzed to better understand such deformation mechanism. The results reveal that the bucking protruding from the edge produces the lower energy needed for EMC laminate.

Heavy metal contents (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) in 99 pairs of soil-rice plant samples were evaluated from the downwind directions of a large thermal power plant in Shaoguan City, Guangdong Province, China. Results indicate that there is a substantial buildup of As, Cd, Cu, Pb, and Zn in the predominant wind direction of the power plant. The significant correlations between S and heavy metals in paddy soil suggest that the power plant represents a source of topsoil heavy metals in Shaoguan City due to sulfur-rich coal burning emissions. Elevated Cd concentrations were also found in rice plant tissues. Average Cd (0.69 mg kg(-1)) and Pb (0.39 mg kg(-1)) contents in rice grain had exceeded their maximum permissible limits (both were 0.2 mg kg(-1)) in foods of China (GB2762-2005). The enrichment of Cd and Pb in rice grain might pose a potential health risk to the local residents.

Comparison tests of needles made in abroad and domestic on chemical composition, microstruture , mechanical property and so on, the main influence factors of the wear resistance were analysed. Approaches of improving the wear resistance of needles are given,such as hot process,surface treatment ,local strengthening. Combined with finite element analysis, the stress and the strain of the needle hook were analysed. Comparative results of both abroad and domestic show that the carbide in the microstructure and structural design of needles are regarded as the main influence factors of the wear resistance.

To study the treatment outcomes of brain-only metastases from small-cell lung cancer (SCLC) at initial diagnose treated by chemotherapy with concurrent brain and thoracic radiotherapy (RT). From Jan 2004 to Jan 2009, 36 treatment-naïve SCLC patients with brain-only metastases in Sun yat-sen University were enrolled. Treatment contained initial EP chemotherapy with concurrent whole-brain radiotherapy (WBRT). EP regimen consisted of etoposide 100 mg/m(2) IV d1-3, cisplatin 80 mg/m(2) IV d1, repeated every 3 weeks. WBRT with total dose of 30 Gy in 10 fractions was started within 1 week from the beginning of chemotherapy followed by thoracic RT including 2 Gy once daily to a total dose of 60 Gy. Treatment responses were evaluated after 3 cycles of chemotherapy. EP regimen was given totally 6 cycles for no tumor progression. Thirty-four patients were evaluable. All of the 20 CNS symptomatic patients experienced symptoms relief. Objective responses in the brain and primary thoracic lesions were observed in 26 (76.5%, 16CR + 10PR) and 29 (85.3%, 23CR + 6PR) patients, respectively. The median survival time (MST) was 19.2 months, and the 1-and 2-year overall survival rates (OS) were 70.6 and 29.4%, respectively, in all patients. Patients with CR response had the longest MST of 21.9 months and 1-and 2-year OS of 93.8 and 43.8%, respectively. Treatment toxicity profiles were acceptable. The treatment strategy of concurrent chemotherapy with brain and thoracic RT might achieve promising survival outcomes comparable to limited-stage SCLC in initially diagnosed SCLC with brain-only metastases.

A variable screening method based on energy flow analysis is provided for significant variables selection in crashworthiness optimizing. Two quantities, significance and specific energy absorption, are used to screen design variables. These quantities are calculated from energy relation matrix and energy absorption of parts. Energy relation matrix is built from finite element crash simulation result to describe energy flow path in parts during impact. The method is applied in the case of a car engine room under frontal impact. Optimization for lightweight using response surface method is performed on the reduced variable set at a relatively low computational cost.

The concentrations, distribution and sources of 16 polycyclic aromatic hydrocarbons (PAHs) were determined in 30 agricultural soil and 16 vegetable samples collected from subtropical Shunde area, an important manufacturing center in China. The total PAHs ranged from 33.7 to 350 microg/kg in soils, and 82 to 1,258 microg/kg in vegetables. The most abundant individual PAHs are phenanthrene, fluoranthene, chrysene, pyrene and benzo(b)fluoranthene for soil samples, and anthracene, naphthalene, phenanthrene, pyrene and chrysene for vegetable samples. Average vegetable-soil ratios of total PAHs were 2.20 for leafy vegetables and 1.27 for fruity vegetables. Total PAHs in vegetable samples are not significantly correlated to those in corresponding soil samples. Principal component analyses were conducted to distinguish samples on basis of their distribution in each town, soil type and vegetable specie. Relatively abundant soil PAHs were found in town Jun'an, Beijiao, Chencun, Lecong and Ronggui, while abundant vegetable PAHs were observed in town Jun'an, Lecong, Xingtan, Daliang and Chenchun. The highest level of total PAHs were found in vegetable soil, followed by pond sediment and "stacked soil" on pond banks. The PAHs contents in leafy vegetables are higher than those in fruity vegetables. Some PAH compound ratios suggest the PAHs derived from incomplete combustion of petroleum, coal and refuse from power generation and ceramic manufacturing, and paint spraying on furniture, as well as sewage irrigation from textile industries. Soil PAHs contents have significant logarithmic correlation with total organic carbon, which demonstrates the importance of soil organic matter as sorbent to prevent losses of PAHs.

Xin-ke Zhang,1,* Tao Qin,1,* Yin-duo Zeng,1,2,* Yuan-yuan Zhao,1 Xue Hou,1 Wen-feng Fang,1 Shao-dong Hong,1 Ting Zhou,1 Zhi-huang Hu,1 Yun-peng Yang,1 Yu-xiang Ma,1 Cong Xue,1 Yan Huang,1 Hong-yun Zhao,1 Li Zhang1 1Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 2Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: To understand the clinicopathological features of patients with primary pulmonary large-cell neuroendocrine carcinoma (LCNEC), including the frequency of epidermal growth factor receptor (EGFR) mutation, and to explore prognostic factors.Methods: We investigated a cohort of 50 individuals from our center database who were diagnosed with operable pulmonary LCNEC and treated in Sun Yat-sen University Cancer Center. Serum albumin (ALB) and neuron-specific enolase (NSE) were also collected. Survival curves were obtained with the Kaplan–Meier method, and the differences between groups in survival were tested by the log-rank test.Results: The median age was 59 years (range, 40–80 years). Fourteen patients underwent mutational analysis of EGFR; of these, 12 had wild-type EGFR and the remaining two had EGFR mutations in exons. The median disease-free survival (DFS) of pulmonary LCNEC was 49.3 months and that of overall survival (OS) was not reached. DFS and OS were shorter for patients with decreased serum ALB than for patients with normal serum ALB (P=0.003 and P=0.004, respectively). Meanwhile, a high level of NSE was also significantly associated with short DFS and OS (P=0.005 and P=0.000, respectively). Multivariate analysis showed that decrease in serum ALB was an independent prognostic factor for OS (P=0.046).Conclusion: The frequency of EGFR mutation in LCNEC patients is low. Serum ALB and NSE levels are valuable prognostic factors for LCNEC patients. Keywords: pulmonary large cell neuroendocrine carcinoma, ALB, NSE, EGFR, prognosis

// Yin-duo Zeng 1, * , Hai Liao 2, * , Tao Qin 1, * , Li Zhang 1 , Wei-dong Wei 3 , Jian-zhong Liang 4 , Fei Xu 1 , Xiao-xiao Dinglin 5 , Shu-xiang Ma 1 , Li-kun Chen 1 1 Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China 2 Lab of Phase I Clinical Study, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China 3 Department of Breast Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China 4 Department of Pathology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China 5 Department of Medical Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China * These authors have contributed equally to this work Correspondence to: Li-kun Chen, e-mail: chenlk@sysucc.org.cn Keywords: Non-small-cell lung cancer, brain metastasis, gefitinib, whole brain radiation therapy, blood brain barrier Received: December 10, 2014 Accepted: January 23, 2015 Published: February 06, 2015 ABSTRACT Introduction To explore the ability of gefitinib to penetrate blood brain barrier (BBB) during whole brain radiation therapy (WBRT). Patients and Methods Enrolled in this study were eligible patients who were diagnosed with BM from NSCLC. Gefitinib was given at 250 mg/day for 30 days, then concurrently with WBRT (40 Gy/20 F/4 w), followed by maintenance. Serial CSF and blood samples were collected on 30 day after gefitinib administration, and at the time of 10, 20, 30 and 40 Gy following WBRT. CSF and plasma samples of 13 patients without BM who were treated with gefitinib were collected as control. CSF and plasma gefitinib levels were measured by LC-MS/MS. Results Fifteen BM patients completed gefitinib plus WBRT. The CSF-to-plasma ratio of gefitinib in patients with BM was higher than that in patients without BM (1.34% vs. 0.36%, P < 0.001). The CSF-to-plasma ratio of gefitinib increased with the increased dose of WBRT and reached the peak (1.87 ± 0.72%) at 30 Gy, which was significantly higher than that 1.34 ± 0.49% at 0 Gy ( P = 0.01). The median time to progression of brain lesions and the median overall survival were 7.07 and 15.4 months, respectively. Conclusion The BBB permeability of gefitinib increased in accordance with escalated dose of WBRT.

Given the use of tamoxifen as standard treatment for hormone receptor&ndash, positive breast cancer, the use of toremifene as an adjuvant endocrine therapy has not been widely examined. The present retrospective study compared the efficacy and safety of toremifene and tamoxifen in the treatment of operable hormone receptor&ndash, positive breast cancer in premenopausal women. Premenopausal patients with hormone receptor&ndash, positive operable breast cancer were eligible. Enrolled patients (n = 1847) received either 60 mg toremifene (n = 396) or 20 mg tamoxifen (n = 1451) daily for a minimum of 5 years after surgery. Disease-free survival (dfs) was the primary endpoint. Overall survival (os) and time to distant recurrence were secondary endpoints. Treatment with toremifene and tamoxifen resulted in no between-group differences in dfs (p = 0.659) or os (p = 0.364). Mean dfs was 10.3 years for both groups. Mean os was 11.2 years for the toremifene group and 11.1 years for tamoxifen group. The 5-year dfs rate was 87.0% in the toremifene group and 85.0% in the tamoxifen group. The 5-year survival rate was 94.3% in the toremifene group and 93.5% in the tamoxifen group. Adverse events rates were similar in the two groups, with the exception of irregular menses, which occurred at a higher rate in the tamoxifen group than in the toremifene group (10.0% vs. 6.3%, p = 0.025). In this retrospective study, the efficacy and safety profiles of toremifene and tamoxifen for the treatment of operable hormone receptor&ndash, positive breast cancer in premenopausal women were similar.

Pemetrexed-based chemotherapy presented about 40 % response rate (RR) on brain lesions of non-small cell lung cancer (NSCLC). But whole brain radiotherapy (WBRT) is still the standard treatment when surgery or radio-surgery is not feasible. This trial evaluated the efficacy and safety and efficacy of pemetrexed-cisplatin plus concurrent WBRT in this population. Forty-two patients were enrolled this study. Patients with newly diagnosed NSCLC with brain metastasis (BM) and performance status (PS) 0-2 were eligible for WBRT. Patients received up to six cycles of cisplatin and pemetrexed (75 and 500 mg/m(2), respectively) every 3 weeks. On day 1-12 during the first cycle of chemotherapy, patients received WBRT 30 Gy/10 fx/12 days. Primary end point was objective RR and progression free survival (PFS) on BM. Secondary end points included extracerebral and overall RR, survival and safety profile. Forty-one were evaluable for response. The histology was all adenocarcinoma. The objective cerebral RR (complete and partial response) in the intent-to-treat population was 68.3 % (28 of 41 patients). Extracerebral and overall RR was 34.1 and 36.6 %, respectively. Progression free survival of BM was 10.6 months, and median overall survival was 12.6 months. The combined treatment with pemetrexed-cisplatin and concurrent WBRT are effective in patients with NSCLC with newly diagnosed BM. This modality of treatment appears to be particularly favorable in RR and progression free survival of BM. Further clinical studies are warranted.

Background: Gefitinib, a tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR), is used both as a single drug and concurrently with whole brain radiotherapy (WBRT) the standard treatment for brain metastases (BM), and is reported to be effective in a few small studies of patients with BM from non-small-cell lung cancer (NSCLC). However, no study has compared the two treatment modalities. This retrospective analysis was conducted to compare the efficacy of gefitinib alone with gefitinib plus concomitant WBRT in treatment of BM from NSCLC. Methods: We retrospectively reviewed 90 patients with BM from NSCLC who received gefitinib alone (250mg/day, gefitinib group) or with concomitant WBRT (40Gy/20f/4w, gefitinib-WBRT group) between September 2005 and September 2009 at Sun Yat-Sen University Cancer Center. Forty-five patients were in each group. Results: The objective response rate of BM was significantly higher in gefitinib-WBRT group (64.4%) compared with gefitinib group (26.7%, P

Porcine epidemic diarrhea virus (PEDV) infection, which causes acute diarrhea and dehydration in suckling piglets, has become a serious problem for the swine industry of China in recent years. In this study, a virulent PEDV strain, GD-1, was obtained from fecal samples from suckling piglets that suffered from severe diarrhea in 2011 in Guangdong, China. Here we describe the complete genome sequence of strain GD-1, which may be helpful in further understanding the molecular epidemiology and genetic diversity of PEDV field isolates in China.