Investigation of the potential role of checkpoint kinase2 in the regulation of gastric cancer stem cells

Purpose: To investigate the potential role of checkpoint kinase2 (CHEK2) in regulating gastric cancer stem cells.Methods: The abnormal features of cellular arrangements in early and advanced stages of gastric cancer were analysed using histology. Immunohistochemistry and Western blotting were used to evaluate the expressions of cancer stem cell markers CD44 and CHEK2 at different stages of gastric cancer.Results: When compared with the control tissue, the size of the cellular nucleus was enlarged as the gastric tumour developed to more advanced stages, and the expression of CD44 increased exponentially. The expression of CHEK2, a protein that regulates cell cycle and apoptosis was aberrantly up-regulated at the early stage of cancer, but as the tumour advanced, its expression became down-regulated.Conclusion: These results show that the higher expression of CHEK2 at the early stages of gastric cancer exerts control over gastric cancer stem cell proliferation. Thus, CHECK2 is a potential target for early treatment of gastric cancer.Keywords: Gastric cancer, CD44, CHEK2, Gastric cancer stem cell

Non-Autoregressive Sentence Ordering

Existing sentence ordering approaches generally employ encoder-decoder frameworks with the pointer net to recover the coherence by recurrently predicting each sentence step-by-step. Such an autoregressive manner only leverages unilateral dependencies during decoding and cannot fully explore the semantic dependency between sentences for ordering. To overcome these limitations, in this paper, we propose a novel Non-Autoregressive Ordering Network, dubbed \textit{NAON}, which explores bilateral dependencies between sentences and predicts the sentence for each position in parallel. We claim that the non-autoregressive manner is not just applicable but also particularly suitable to the sentence ordering task because of two peculiar characteristics of the task: 1) each generation target is in deterministic length, and 2) the sentences and positions should match exclusively. Furthermore, to address the repetition issue of the naive non-autoregressive Transformer, we introduce an exclusive loss to constrain the exclusiveness between positions and sentences. To verify the effectiveness of the proposed model, we conduct extensive experiments on several common-used datasets and the experimental results show that our method outperforms all the autoregressive approaches and yields competitive performance compared with the state-of-the-arts. The codes are available at: \url{https://github.com/steven640pixel/nonautoregressive-sentence-ordering}.Comment: Accepted at Findings of EMNLP202

The linear and nonlinear Jaynes-Cummings model for the multiphoton transition

With the Jaynes-Cummings model, we have studied the atom and light field quantum entanglement of multiphoton transition, and researched the effect of initial state superposition coefficient $C_{1}$, the transition photon number $N$, the quantum discord $\delta$ and the nonlinear coefficient $\chi$ on the quantum entanglement degrees. We have given the quantum entanglement degrees curves with time evolution, and obtained some results, which should have been used in quantum computing and quantum information.Comment: arXiv admin note: text overlap with arXiv:1404.0821, arXiv:1205.0979 by other author

Combined PD-1 blockade and GITR triggering induce a potent antitumor immunity in murine cancer models and synergizes with chemotherapeutic drugs

BACKGROUND: The coinhibitory receptor Programmed Death-1 (PD-1) inhibits effector functions of activated T cells and prevents autoimmunity, however, cancer hijack this pathway to escape from immune attack. The costimulatory receptor glucocorticoid-induced TNFR related protein (GITR) is up-regulated on activated T cells and increases their proliferation, activation and cytokine production. We hypothesize that concomitant PD-1 blockade and GITR triggering would synergistically improve the effector functions of tumor-infiltrating T cells and increase the antitumor immunity. In present study, we evaluated the antitumor effects and mechanisms of combined PD-1 blockade and GITR triggering in a clinically highly relevant murine ID8 ovarian cancer model. METHODS: Mice with 7 days-established peritoneal ID8 ovarian cancer were treated intraperitoneally (i.p.) with either control, anti-PD-1, anti-GITR or anti-PD-1/GITR monoclonal antibody (mAb) and their survival was evaluated; the phenotype and function of tumor-associated immune cells in peritoneal cavity of treated mice was analyzed by flow cytometry, and systemic antigen-specific immune response was evaluated by ELISA and cytotoxicity assay. RESULTS: Combined anti-PD-1/GITR mAb treatment remarkably inhibited peritoneal ID8 tumor growth with 20% of mice tumor free 90 days after tumor challenge while treatment with either anti-PD-1 or anti-GITR mAb alone exhibited little antitumor effect. The durable antitumor effect was associated with a memory immune response and conferred by CD4(+) cells and CD8(+) T cells. The treatment of anti-PD-1/GITR mAb increased the frequencies of interferon-γ-producing effector T cells and decreased immunosuppressive regulatory T cells and myeloid-derived suppressor cells, shifting an immunosuppressive tumor milieu to an immunostimulatory state in peritoneal cavity. In addition, combined treatment of anti-PD-1/GITR mAb mounted an antigen-specific immune response as evidenced by antigen-specific IFN-γ production and cytolytic activity of spleen cells from treated mice. More importantly, combined treatment of anti-PD-1/GITR mAb and chemotherapeutic drugs (cisplatin or paclitaxel) further increased the antitumor efficacy with 80% of mice obtaining tumor-free long-term survival in murine ID8 ovarian cancer and 4 T1 breast cancer models. CONCLUSIONS: Combined anti-PD-1/GITR mAb treatment induces a potent antitumor immunity, which can be further promoted by chemotherapeutic drugs. A combined strategy of anti-PD-1/GITR mAb plus cisplatin or paclitaxel should be considered translation into clinic