| 1 | Th1 cytokines promote T-cell binding to antigen-presenting cells via enhanced hyaluronan production and accumulation at the immune synapse显示文摘Hyaluronan(HA)production by dendritic cells(DCs)is known to promote antigen presentation and to augment T-cell activation and proliferation.We hypothesized that pericellular HA can function as intercellular‘glue’directly mediating T cell–DC binding.Using primary human cells,we observed HA-dependent binding between T cells and DCs,which was abrogated upon pre-treatment of the DCs with 4-methylumbelliferone(4-MU),an agent which blocks HA synthesis.Furthermore,T cells regulate HA production by DCs via T cell-derived cytokines in a T helper(Th)subset-specific manner,as demonstrated by the observation that cell-culture supernatants from Th1 but not Th2 clones promote HA production.Similar effects were seen upon the addition of exogenous Th1 cytokines,IL-2,interferon c(IFN-c)and tumor necrosis factor a(TNF-a).The critical factors which determined the extent of DC–T cell binding in this system were the nature of the pre-treatment the DCs received and their capacity to synthesize HA,as T-cell clones which were pre-treated with monensin,added to block cytokine secretion,bound equivalently irrespective of their Th subset.These data support the existence of a feedforward loop wherein T-cell cytokines influence DC production of HA,which in turn affects the extent of DC–T cell binding.We also document the presence of focal deposits of HA at the immune synapse between T-cells and APC and on dendritic processes thought to be important in antigen presentation.These data point to a pivotal role for HA in DC–T cell interactions at the IS. | Paul L Bollyky Stephen P Evanko Rebecca P Wu Susan Potter-Perigo S Alice Long Brian Kinsella Helena Reijonen Kelly Guebtner Brandon Teng Christina K Chan Kathy R Braun John A Gebe Gerald T Nepom Thomas N Wight | 2010 | Cellular & Molecular Immunology2010,7,3: | 3 |
| 17 | Racial/ethnic disparities in hepatocellular carcinoma treatment and survival in California, 1988-2012显示文摘AIM To describe racial/ethnic differences in treatment and survival among liver cancer patients in a populationbased cancer registry.METHODS Invasive cases of primary hepatocellular carcinoma, n = 33270, diagnosed between January 1, 1988-December 31, 2012 and reported to the California Cancer Registry were analyzed by race/ethnicity, age, gender, geographical region, socio-economic status, time period of diagnosis, stage, surgical treatment, and survival. Patients were classified into 15 racial/ethnic groups: non-Hispanic White(White, n = 12710), Hispanic(n = 8500), Chinese(n = 2723), non-Hispanic Black(Black, n = 2609), Vietnamese(n = 2063), Filipino(n = 1479), Korean(n = 1099), Japanese(n = 658), American Indian/Alaskan Native(AIAN, n = 281), Laotian/Hmong (n = 244), Cambodian(n = 233), South Asian(n = 190), Hawai`ian/Pacific Islander(n = 172), Thai(n = 95), and Other Asian(n = 214). The main outcome measures were receipt of surgical treatment, and cause-specific and all-cause mortality.RESULTS After adjustment for socio-demographic characteristics, time period, and stage of disease, compared to Whites, Laotian/Hmong [odds ratio(OR) = 0.30, 95%CI: 0.17-0.53], Cambodian(OR = 0.65, 95%CI: 0.45-0.96), AIAN(OR = 0.66, 95%CI: 0.46-0.93), Black(OR = 0.76, 95%CI: 0.67-0.86), and Hispanic(OR = 0.78, 95%CI: 0.72-0.84) patients were less likely, whereas Chinese(OR = 1.58, 95%CI: 1.42-1.77), Koreans(OR = 1.45, 95%CI: 1.24-1.70), Japanese(OR = 1.41, 95%CI: 1.15-1.72), and Vietnamese(OR = 1.26, 95%CI: 1.12-1.42) were more likely to receive surgical treatment. After adjustment for the same covariates and treatment, cause-specific mortality was higher for Laotian/Hmong [(hazard ratio(HR) = 1.50, 95%CI: 1.29-1.73)], Cambodians(HR = 1.35, 95%CI: 1.16-1.58), and Blacks(HR = 1.07, 95%CI: 1.01-1.13), and lower for Chinese(HR = 0.82, 95%CI: 0.77-0.86), Filipinos(HR = 0.84, 95%CI: 0.78-0.90), Vietnamese(HR = 0.85, 95%CI: 0.80-0.90), Koreans(HR = 0.90, 95%CI: 0.83-0.97), and Hispanics(HR = 0.91, 95%CI: 0.88-0.94); results were similar for all-cause mortality.CONCLUSION Disaggregated data revealed substantial racial/ethnic differences in liver cancer treatment and survival, demonstrating the need for development of targeted interventions to mitigate disparities. | Susan L Stewart Sandy L Kwong Christopher L Bowlus Tung T Nguyen Annette E Maxwell Roshan Bastani Eric W Chak Moon S Chen Jr | 2016 | World Journal of Gastroenterology2016,22,38: | 1 |