Latest therapeutic target for gastric cancer:Anthrax toxin receptor 1

Anthrax toxin receptor 1(ANTXR1),also known as tumor endothelial marker 8,is a highly conserved cell surface protein overexpressed in tumor-infiltrating vessels.It was first found in vascular endothelial cells of human colorectal cancer.Although our understanding of its physiological function is limited,it has been found that ANTXR1 binds collagen and promotes migration of endothelial cells in vitro.ANTXR1 is upregulated in vessels of different tumor types in mice and humans,and is also expressed by tumor cells themselves in some tumors,such as gastric,lung,intestinal and breast cancer.Developmental angiogenesis and wound healing were not disturbed in ANTXR1 knockout mice,but compared with wild-type mice,growth of melanoma was impaired after ANTXR1 knockout,indicating that host-derived ANTXR1 can promote tumor growth on the basis of immune activity.Previous studies have shown that ANTXR1 vaccines or sublethal doses of anthrax toxin can inhibit angiogenesis,slow tumor growth and prolong survival.These studies suggest that ANTXR1 is necessary for tumor rather than physiological angiogenesis.It has been found that ANTXR1 plays an important role in tumor angiogenesisas well as in the growth and metastasis of many kinds of tumors.This article reviews the physiological function of ANTXR1 and its role in different kinds of cancer.

Salvage irrigation-suction in gracilis muscle repair of complex rectovaginal and rectourethral fistulas

AIM:To evaluate the efficacy of gracilis muscle transposition and postoperative salvage irrigation-suction in the treatment of complex rectovaginal fistulas(RVFs)and rectourethral fistulas(RUFs).METHODS:Between May 2009 and March 2012,11female patients with complex RVFs and 8 male patients with RUFs were prospectively enrolled.Gracilis muscle transposition was undertaken in all patients and postoperative wound irrigation-suction was performed in patients with early leakage.Efficacy was assessed in terms of the success rate and surgical complications.SF-36 quality of life(QOL)scores and Wexner fecal incontinence scores were compared before and after surgery.RESULTS:The fistulas healed in 14 patients after gracilis muscle transposition;the initial healing rate was73.7%.Postoperative leakage occurred and continuous irrigation-suction of wounds was undertaken in 5patients:4 healed and 1 failed,and postoperative fecal diversions were performed for the patient whose treatment failed.At a median follow-up of 17 mo,the overall healing rate was 94.7%.Postoperative complications occurred in 4 cases.Significant improvement was observed in the quality outcomes framework scores(P<0.001)and Wexner fecal incontinence scores(P=0.002)after the successful healing of complex RVFs or RUFs.There was no significant difference in SF-36 QOL scores between the initial healing group and irrigationsuction-assisted healing group.CONCLUSION:Gracilis muscle transposition and postoperative salvage wound irrigation-suction gained a high success rate in the treatment of complex RVFs and RUFs.QOL and fecal incontinence were significantly improved after the successful healing of RVFs and RUFs.

Correlation study between helicobacter pylori infection and tumor malignancy in patients with gastric cancer

Objective:To study the correlation between helicobacter pylori infection and tumor malignancy in patients with gastric cancer.Methods:A total of 119 patients with gastric cancer treated in our hospital between May 2013 and December 2015 were collected and divided into HP-positive group (n=89) and HP-negative group (n=30) according to the combination of helicobacter pylori infection or not. RIA method was used to detect the serum angiogenesis index levels;fluorescence quantitative PCR (RT-PCR) was used to detect the mRNA expression of autophagy genes and proliferation genes in tumor tissues.Results:Serum angiogenesis indexes bFGF, VEGF and MMP-9 levels of HP-positive group were significantly higher than those of HP-negative groups;autophagy genes Beclin1, BNIP3, pULK and PI3KC3 mRNA expression in tumor tissues of HP-positive group were significantly lower than those of HP-negative group, pro-apoptotic genes Bax and p53 mRNA expression were significantly lower than those of HP-negative group, and anti-apoptotic genes PIK3CD, CIP2A and I2PP2A mRNA expression were significantly higher than those of HP-negative group. Conclusion:Helicobacter pylori infection can promote angiogenesis and cell proliferation in lesions of patients with gastric cancer.

DyPipe: A Holistic Approach to Accelerating Dynamic Neural Networks with Dynamic Pipelining

Dynamic neural network(NN)techniques are increasingly important because they facilitate deep learning techniques with more complex network architectures.However,existing studies,which predominantly optimize the static computational graphs by static scheduling methods,usually focus on optimizing static neural networks in deep neural network(DNN)accelerators.We analyze the execution process of dynamic neural networks and observe that dynamic features introduce challenges for efficient scheduling and pipelining in existing DNN accelerators.We propose DyPipe,a holistic approach to optimizing dynamic neural network inferences in enhanced DNN accelerators.DyPipe achieves significant performance improvements for dynamic neural networks while it introduces negligible overhead for static neural networks.Our evaluation demonstrates that DyPipe achieves 1.7x speedup on dynamic neural networks and maintains more than 96%performance for static neural networks.

Palladium-Catalyzed C-C Bond Activation/Suzuki Reaction of Methylenecyclobutanes

Transition-metal catalyzed C-C bond activation is a formidable challenge owing to the high bond energy.We report here a novel palladium-catalyzed C-C bond activation manner of methylenecyclobutanes followed by subsequent Suzuki cross-coupling reaction affording multisubstituted indanes.The tandem reaction process involves intramolecular carbopalladation of double bond,β-carbon elimination and intermolecular trapping of the transient a-alkylpalladium complex with boronic acids.A new TADDOL-derived phos-phoramidite ligand bearing fluorine and silicon-based bulky groups is found to be efficient for C-C bond activation of methylenecyclobutanes.

Analysis of cyclin E co-expression genes reveals nuclear transcription factor Y subunit alpha is an oncogene in gastric cancer

Objective: To explore genes potentially co-expressed with cyclin E in gastric cancer and discover possible targets for gastric cancer treatment. Methods: The Cancer Genome Atlas (TCGA) stomach adenocarcinoma sequencing data were used to predict genes co-expressed with cyclin E. Co-expression genes predicted by cBioPortal online analysis with Pearson correlation coefficient ≥0.4 were analyzed by gene ontology (GO) enrichment annotation using the PANTHER online platform (Ver. 7). Interactions between proteins encoded by these genes were analyzed using the STRING online platform (Ver. 10.5) and Cytoscape software (Ver. 3.5.1). Genes displaying a high degree of connection were analyzed by transcription factor enrichment prediction using FunRich software (Ver. 3). The significant transcription factor and cyclin E expression levels and their impact on gastric cancer progression were analyzed by Western blotting and Kaplan-Meier survival curve analysis. Results: After filtering the co-expression gene prediction results, 78 predicted genes that included 73 protein coding genes and 5 non-coding genes with Pearson correlation coefficient ≥0.4 were selected. The expressions of the genes were considered to be correlated with cyclin E expression. Among the 78 genes co-expressed with cyclin E, 19 genes at the central of the regulatory network associated with cyclin E were discovered. Nuclear transcription factor Y subunit alpha (NF-YA) was identified as a significant transcription factor associated with cyclin E co-expressing genes. Analysis of specimen donors’ clinical records revealed that high expression of NF-YA tended to be associated with increased cyclin E expression. The expression of both was associated with progression of gastric cancer. Western blotting results showed that compared with normal tissues, NF-YA and cyclin E were highly expressed in tumor tissues (P < 0.001). Survival curve analysis clearly demonstrated relatively poor overall survival of gastric cancer patients with high cyclin E or high NF-YA expression level, compared to patients with low cyclin E or NF-YA expression (P < 0.05). Conclusions: NF-YA may promote gastric cancer progression by increasing the transcription of cyclin E and other cell cycle regulatory genes. NF-YA might be a potential therapeutically useful prognostic factor for gastric cancer.

中国胃癌患者肿瘤遗传易感基因的多中心研究

背景:10%的胃癌与遗传因素相关。然而,对中国胃癌患者遗传易感基因的认识仍极为匮乏。本研究旨在确定中国人群中具有遗传高危因素的胃癌患者的遗传易感基因突变频率和突变谱。方法:纳入来自中国7家中心具有家族遗传性高危因素的40例胃癌患者,采用二代测序技术检测先证者与癌症遗传易感性相关的171个基因。对于发现存在已知致病或疑似致病突变的先证者,使用一代测序技术对先证者及其血亲进行突变位点的进一步验证。结果:40例患者中,有25%(10/40)先证者发现了涉及9个不同基因的10种已知致病或疑似致病突变,包括1例CDH1,1例MLH1,1例MSH2,1例CHEK2,1例BLM,1例EXT2,1例PALB2,1例ERCC2突变,2例SPINK1。此外,在27例患者中发现了129个意义未明的突变。结论:本研究显示,在具备遗传高危因素的中国胃癌患者中,每4例患者就有1例存在遗传易感基因的已知致病或疑似致病胚系突变。本研究结果进一步表明,中国胃癌患者可能具有独特的遗传背景。

Preclinical studies of the triazolo[1,5-a]pyrimidine derivative WS-716 as a highly potent,specific and orally active P-glycoprotein(P-gp)inhibitor

Multidrug resistance(MDR) is the main cause of clinical treatment failure and poor prognosis in cancer. Targeting P-glycoprotein(P-gp) has been regarded as an effective strategy to overcome MDR. In this work, we reported our preclinical studies of the triazolo[1,5-a]pyrimidine-based compound WS-716 as a highly potent, specific, and orally active P-gp inhibitor. Through direct binding to P-gp,WS-716 inhibited efflux function of P-gp and specifically reversed P-gp-mediated MDR to paclitaxel(PTX) in multiple resistant cell lines, without changing its expression or subcellular localization. WS-716 and PTX synergistically inhibited formation of colony and 3D spheroid, induced apoptosis and cell cycle arrest at G2/M phase in resistant SW620/Ad300 cells. In addition, WS-716 displayed minimal effect on the drug-metabolizing enzyme cytochrome P4503A4(CYP3A4). Importantly, WS-716 increased sensitivity of both pre-clinically and clinically derived MDR tumors to PTX in vivo with the T/C value of 29.7% in patient-derived xenograft(PDX) models. Relative to PTX treatment alone, combination of WS-716 and PTX caused no obvious adverse reactions. Taken together, our preclinical studies revealed therapeutic promise of WS-716 against MDR cancer, the promising data warrant its further development for cancer therapy.

Tetris:A Heuristic Static Memory Management Framework for Uniform Memory Multicore Neural Network Accelerators

Uniform memory multicore neural network accelerators(UNNAs)furnish huge computing power to emerging neural network applications.Meanwhile,with neural network architectures going deeper and wider,the limited memory capacity has become a constraint to deploy models on UNNA platforms.Therefore how to efficiently manage memory space and how to reduce workload footprints are urgently significant.In this paper,we propose Tetris:a heuristic static memory management framework for UNNA platforms.Tetris reconstructs execution flows and synchronization relationships among cores to analyze each tensor’s liveness interval.Then the memory management problem is converted to a sequence permutation problem.Tetris uses a genetic algorithm to explore the permutation space to optimize the memory management strategy and reduce memory footprints.We evaluate several typical neural networks and the experimental results demonstrate that Tetris outperforms the state-of-the-art memory allocation methods,and achieves an average memory reduction ratio of 91.9%and 87.9%for a quad-core and a 16-core Cambricon-X platform,respectively.

Preparation and optical properties of tin dioxide inverse opal film

As a novel structure, inverse opal, with threedimensional periodic macropore and mesopore and huge specific surface area, has great promising applications. In this paper, tin dioxide (SnO_(2)) inverse opal films were prepared with sol–gel method by cooperative opal template. The surface morphologies of SnO_(2)inverse opal films were examined by scanning electron microscopy (SEM), the inner structure of SnO_(2)inverse opal films was examined by transmission electron microscopy (TEM), the optical properties of SnO_(2)inverse opal films were studied and discussed in detail. Optical reflectance spectra reveal that, for the opal films, the wavelengths of the reflectance peak confirmed by the experimental reflectance spectra are consistent with the theoretical values;for the SnO_(2)inverse opal films, the wavelengths of the reflectance peak confirmed by the experimental reflectance spectra deviate from theoretical values largely.

Effects of cisplatin in combination with hyperthermia on biological characteristics of retroperitoneal liposarcoma

Pathologically,retroperitoneal liposarcoma(RPLS)is a group of malignant tumors,which originates from adipose tissue in retroperitoneal space,accounting for almost 70%of all retroperitoneal tumors.RPLS has no optimal treatment.Surgical resection(R_(0)/R_(1))is the most effective therapy;however,recurrence rate is very high.Grossly incomplete surgical resection(R_(2))is an important risk factor for early recurrence of RPLS.