These data show that apatinib treatment significantly improved OS and PFS with an acceptable safety profile in patients with advanced gastric cancer refractory to two or more lines of prior chemotherapy.

This study provides the first description of increased expression of miR-155 in H. pylori infection, and miR-155 may function as novel negative regulator that help to fine-tune the inflammation response of H. pylori infection.

The direct amplification of plasma miR-221 can be used as a potential noninvasive molecular marker for diagnosis and prognosis of CRC and is correlated with p53 expression.

CD4+ T cell responses are critical for the pathogenesis of Helicobacter pylori infection. The present study evaluated the role of the Th17 subset in H. pylori infection. H. pylori infection induced significant expression of IL-17 and IFN-g in mouse gastric tissue. IL-23 and IL-12 were increased in the gastric tissue and in H. pylori-stimulated macrophages. Cell responses were examined by intracellular staining for IFN-g, IL-4, and IL-17. Mice infected with H. pylori developed a mixed Th17/Th1 response; Th17 responses preceded Th1 responses. Treatment of mice with an anti-IL-17 Ab but not a control Ab significantly reduced the H. pylori burden and inflammation in the stomach. H. pylori colonization and gastric inflammation were also lower in IL-17 2/2 mice. Furthermore, administration of recombinant adenovirus encoding mouse IL-17 increased both H. pylori load and inflammation. Further analysis showed that the Th1 cell responses to H. pylori were downregulated when IL-17 is deficient. These results together suggest that H. pylori infection induces a mixed Th17/Th1 cell response and the Th17/IL-17 pathway modulates Th1 cell responses and contributes to pathology. The Journal of Immunology, 2010, 184: 5121-5129. H elicobacter pylori is a Gram-negative, microaerophilic bacterium that resides extracellularly in the gastric mucosa and infects .50% of the population worldwide. H. pyloriinduced chronic inflammation is the cause of gastritis and peptic ulcers and a risk factor for gastric cancer (1, 2). H. pylori infection causes severe local inflammation in the gastric mucosa. CD3 + CD4 + T cells are increased in infected gastric lamina propria and play important roles in the pathogenesis of persistent H. pylori infection (3). Traditionally, CD4 + T cells are classified into two main classes: Th1 and Th2, on the basis of their cytokine secretion and immune regulatory function. Th1 cells secrete IFN-g, IL-2, and IL-12 and regulate cellular immunity, whereas Th2 cells produce IL-4, IL-5, and IL-13 and mediate humoral responses. To date, studies of immune responses to H. pylori have largely focused on Th1 and Th2 cells, and it is generally accepted that H. pylori infection results in a Th1-dominant response and that gastric inflammation largely depends on Th1 cell responses (3-6); however, IFN-g secretion alone is insufficient to induce gastritis (3). Thus, the detailed mechanism of pathogenesis is not clear. A novel subset of effector T cells, identified by secretion of IL-17, has been defined as Th17 cells. Th17 cells are distinct from Th1 and Th2 cells in their differentiation and function (7,8). TGF-b and IL-6 from activated macrophages/dendritic cells are required for Th17 cell differentiation in murine systems (9), whereas IL-12 and IFN-g promote Th1 cell development and IL-4 primes Th2 cell differentiation. The expansion and survival of Th17 cells are promoted by IL-23 (9), a heterodimeric cytokine composed of a unique p19 subunit and a p40 subunit shared with IL-12 (10). The identification of Th17 cells necessit...

ObjectiveHelper T (Th) cell responses are critical for the pathogenesis of Helicobacter pylori-induced gastritis. Th22 cells represent a newly discovered Th cell subset, but their relevance to H. pylori-induced gastritis is unknown.DesignFlow cytometry, real-time PCR and ELISA analyses were performed to examine cell, protein and transcript levels in gastric samples from patients and mice infected with H. pylori. Gastric tissues from interleukin (IL)-22-deficient and wild-type (control) mice were also examined. Tissue inflammation was determined for pro-inflammatory cell infiltration and pro-inflammatory protein production. Gastric epithelial cells and myeloid-derived suppressor cells (MDSC) were isolated, stimulated and/or cultured for Th22 cell function assays.ResultsTh22 cells accumulated in gastric mucosa of both patients and mice infected with H. pylori. Th22 cell polarisation was promoted via the production of IL-23 by dendritic cells (DC) during H. pylori infection, and resulted in increased inflammation within the gastric mucosa. This inflammation was characterised by the CXCR2-dependent influx of MDSCs, whose migration was induced via the IL-22-dependent production of CXCL2 by gastric epithelial cells. Under the influence of IL-22, MDSCs, in turn, produced pro-inflammatory proteins, such as S100A8 and S100A9, and suppressed Th1 cell responses, thereby contributing to the development of H. pylori-associated gastritis.ConclusionsThis study, therefore, identifies a novel regulatory network involving H. pylori, DCs, Th22 cells, gastric epithelial cells and MDSCs, which collectively exert a pro-inflammatory effect within the gastric microenvironment. Efforts to inhibit this Th22-dependent pathway may therefore prove a valuable strategy in the therapy of H. pylori-associated gastritis.

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MicroRNAs are a new class of non-proteincoding, small RNAs that function as tumor suppressors or oncogenes. They participate in diverse biological pathways and function as gene regulators. A G>C polymorphism (rs2910164), which is located in the sequence of miR-146a precursor, results in a change from G:U to C:U in its stem region. However, it remains largely unknown whether this single nucleotide polymorphism (SNP) may alter esophageal squamous cell carcinoma (ESCC) susceptibility. In the current study, we evaluated association between rs2910164 and ESCC susceptibility in a case-control study of 444 sporadic ESCC patients and 468 matched cancer-free controls in a Chinese Han population. Compared with rs2910164 variant genotype CC, genotype GG was associated with increased risk of ESCC (Odds Ratio, 2.39, 95% Confidence Interval, 1.36-4.20). In the smokers, the risk of rs2910164 GG genotype was more notable (Odds Ratio, 3.17, 95% Confidence Interval, 1.71-4.46). In the stratification analyses, we also found there was a strong correlation between rs2910164 C/G variant and the clinical TNM stage (P < 0.01). These findings suggest that this functional SNP in pre-miR-146a could contribute to ESCC susceptibility and clinical outcome.

A cross-sectional study was conducted among 249 Chinese cancer patients with multiple diagnoses to validate a Chinese version of the Brief Fatigue Inventory (BFI-C). Cronbach's coefficient alpha was 0.92 for fatigue severity items and 0.90 for fatigue interference items. Construct validity was explored by principal factor analysis and suggested a two-factor solution: fatigue severity and fatigue interference. Internal consistency reliability was excellent. Convergent validity was examined by correlating the BFI-C with 2 subscales and 2 component scores of the MOS 36-Item Short-Form Health Survey (coefficients ranged between -0.44 and -0.71, P<0.001). Known-group validity was examined by comparing fatigue severity in patients having different scores on the Eastern Cooperative Oncology Group Performance Status Scale. Approximately 60% of patients experienced moderate to severe fatigue (4 or greater on the 0-10 scale of the BFI-C "fatigue worst" item). The BFI-C is a valid, reliable instrument to measure the severity and impact of cancer-related fatigue among Chinese patients.