70 research outputs found

    Analysis of group 12a lymph node metastasis at different sites of gastric adenocarcinoma and its risk factors

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    Background and purpose: It is not clear that the pattern of lymph node (group 12a) metastasis within the hepatoduodenal ligament (along the hepatic artery) in gastric cancer, its indications for dissection are still controversial, and there is a lack of relevant clinical study data from large samples. This study investigated the risk factors of lymph node group 12a metastasis in gastric cancer at different sites by observing the lymph node metastasis rate. Methods: The medical records of 1 112 gastric cancer patients admitted to the Department of Gastric Surgery in Henan Provincial People’s Hospital from May 2016 to July 2021 were retrospectively analyzed. According to tumor location, they were divided into upper gastric cancer (561 cases), gastric body cancer (224 cases) and gastric antrum cancer (327 cases). The lymph node metastasis rate of group 12a in patients with different parts of gastric cancer was recorded. The c2 test and Fisher’s exact probability test were used to compare the relationship between group 12a lymph node metastasis and clinicopathological features in patients with gastric cancer at different sites. Multivariate logistic regression analysis was used to analyze the risk factors of group 12a lymph node metastasis in patients with gastric cancer at different locations. Results: Group 12a lymph node metastasis occurred in 72 of 1 112 gastric cancer patients, and the overall metastatic rate was 6.5%. Among the 561 cases of upper gastric cancer, 25 cases developed group 12a lymph node metastasis, and the metastatic rate was 4.5%. Of the 224 patients with gastric body cancer, 17 cases were positive in group 12a lymph nodes, and the metastasis rate was 7.6%. Among the 327 cases of gastric antrum cancer, 30 cases were positive in group 12a lymph nodes, and the metastatic rate was 9.2%. Taking the lymph node metastasis in group 12a as the dependent variable, and taking the indicators with statistical significance in univariate analysis as independent variables, they were included in the model for multivariate logistic regression analysis. The results showed that tumor diameter (OR=3.122, 95% CI: 2.896-3.366, P<0.001), T stage (OR=2.406, 95% CI: 1.705-3.396, P<0.001), TNM stage (OR=7.910, 95% CI: 4.755-13.160, P<0.001) were risk factors for lymph node metastasis in group 12a of upper gastric cancer patients. Tumor diameter (OR=2.757, 95% CI: 2.495-3.047, P<0.001), T stage (OR=3.298, 95% CI: 2.346-4.638, P<0.001), vascular nerve invasion (OR=1.839, 95% CI: 1.368-2.473, P<0.001) were risk factors for lymph node metastasis in group 12a of patients with gastric body cancer. Body mass index (BMI) (OR=1.098, 95% CI: 1.023-1.178, P=0.010), tumor diameter (OR=2.865, 95% CI: 1.778-4.616, P<0.001), T stage (OR=13.497, 95% CI: 8.363-21.783, P<0.001), TNM stage (OR=3.806, 95% CI: 3.113-4.653, P<0.001) were risk factors for lymph node metastasis in group 12a of patients with gastric antrum cancer. Conclusion: The total lymph node metastasis rate in group 12a is low. Tumor size, invasion depth, N stage and tumor stage are independent risk factors for group 12a lymph node metastasis in gastric cancer. Besides, vascular nerve invasion is the independent risk factors for gastric body cancer. Gastric body cancer and gastric antrum cancer require routine dissection of group 12a lymph nodes. The metastatic rate of lymph nodes in group 12a of upper gastric cancer is low, and routine dissection is not required. However, when the diameter is ≥6 cm, the depth of tumor invasion is deep (T3-T4), and the tumor stage is late (Ⅲ-Ⅳ), group 12a lymph nodes need to be dissected

    Lower gut abundance of Eubacterium rectale is linked to COVID-19 mortality

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    IntroductionEmerging preclinical and clinical studies suggest that altered gut microbiome composition and functions are associated with coronavirus 2019 (COVID- 19) severity and its long-term complications. We hypothesize that COVID-19 outcome is associated with gut microbiome status in population-based settings.MethodsGut metagenomic data of the adult population consisting of 2871 subjects from 16 countries were obtained from ExperimentHub through R, while the dynamic death data of COVID-19 patients between January 22, 2020 and December 8, 2020 in each country was acquired from Johns Hopkins Coronavirus Resource Center. An adjusted stable mortality rate (SMR) was used to represent these countries’ mortality and correlated with the mean relative abundance (mRA) of healthy adult gut microbiome species.ResultsAfter excluding bacterial species with low prevalence (prevalence <0.2 in the included countries), the β-diversity was significantly higher in the countries with high SMR when compared with those with median or low SMR (p <0.001). We then identified the mRA of two butyrate producers, Eubacterium rectale and Roseburia intestinalis, that were negatively correlated with SMR during the study period. And the reduction of these species was associated with severer COVID-19 manifestation.ConclusionPopulation-based microbiome signatures with the stable mortality rate of COVID-19 in different countries suggest that altered gut microbiome composition and functions are associated with mortality of COVID-19

    31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

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    Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

    Long non-coding RNA CCHE1 modulates LDHA-mediated glycolysis and confers chemoresistance to melanoma cells

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    Abstract Melanoma is considered as the most common metastatic skin cancer with increasing incidence and high mortality globally. The vital roles of long non-coding RNAs (lncRNAs) in the tumorigenesis of melanoma are elucidated by emerging evidence. The lncRNA cervical carcinoma high-expressed 1 (CCHE1) was overexpressed and acted as an oncogene in a variety of cancers, while the function of CCHE1 in melanoma remains unclear. Here, we found that CCHE1 was highly expressed in melanoma and correlated with the poorer survival of melanoma patients. Depletion of CCHE1 inhibited the proliferation, induced cell apoptosis and suppressed in vivo tumor growth. To further understand the functional mechanism of CCHE1, the interacting partners of CCHE1 were identified via RNA pull-down assay followed by mass spectrometry. CCHE1 was found to bind lactate dehydrogenase A (LDHA) and acted as a scaffold to enhance the interaction of LDHA with the fibroblast growth factor receptor type 1 (FGFR1), which consequently enhanced LDHA phosphorylation and activity of LDHA. Inhibiting CCHE1 strikingly suppressed the glycolytic flux of melanoma cells and lactate generation in vivo. Further study demonstrated that CCHE1 desensitized melanoma cells to dacarbazine and inhibition of glycolysis reversed CCHE1-induced chemoresistance. These results uncovered the novel function of CCHE1 in melanoma by reprogramming the glucose metabolism via orchestrating the activity of LDHA

    Spatiotemporal Patterns and Morphological Characteristics of <i>Ulva prolifera</i> Distribution in the Yellow Sea, China in 2016–2018

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    The world&#8217;s largest macroalgal blooms, Ulva prolifera, have appeared in the Yellow Sea every summer on different scales since 2007, causing great harm to the regional marine economy. In this study, the Normalized Difference of Vegetation Index (NDVI) index was used to extract the green tide of Ulva prolifera from MODIS images in the Yellow Sea in 2016&#8315;2018, to investigate its spatiotemporal patterns and to calculate its occurrence probability. Using the standard deviational ellipse (SDE), the morphological characteristics of the green tide, including directionality and regularity, were analyzed. The results showed that the largest distribution and coverage areas occurred in 2016, with 57,384 km2 and 2906 km2, respectively and that the total affected region during three years was 163,162 km2. The green tide drifted northward and died out near Qingdao, Shandong Province, which was found to be a high-risk region. The coast of Jiangsu Province was believed to be the source of Ulva prolifera, but it was probably not the only one. The regularity of the boundary shape of the distribution showed a change that was opposite to the variation of scale. Several sharp increases were found in the parameters of the SDE in all three years. In conclusion, the overall situation of Ulva prolifera was still severe in recent years, and the sea area near Qingdao became the worst hit area of the green tide event. It was also shown that the sea surface wind played an important part in its migration and morphological changes
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