Histopathological Imaging–Environment Interactions in Cancer Modeling

Histopathological imaging has been routinely conducted in cancer diagnosis and recently used for modeling other cancer outcomes/phenotypes such as prognosis. Clinical/environmental factors have long been extensively used in cancer modeling. However, there is still a lack of study exploring possible interactions of histopathological imaging features and clinical/environmental risk factors in cancer modeling. In this article, we explore such a possibility and conduct both marginal and joint interaction analysis. Novel statistical methods, which are “borrowed” from gene–environment interaction analysis, are employed. Analysis of The Cancer Genome Atlas (TCGA) lung adenocarcinoma (LUAD) data is conducted. More specifically, we examine a biomarker of lung function as well as overall survival. Possible interaction effects are identified. Overall, this study can suggest an alternative way of cancer modeling that innovatively combines histopathological imaging and clinical/environmental data

Can 9q34.2 rs633862 polymorphism predict survival in epithelial ovarian cancer?

Objective Our previous genome-wide association study (GWAS) identified that the ABO rs633862 variant in chromosome 9q34.2 was associated with the risk of epithelial ovarian cancer (EOC) in Chinese Han women. The aim of the present study was to evaluate its prognostic effect on EOC. Methods A total of 669 EOC patients were enrolled for the genotyping of rs633862 variant in 9q34.2. We used Kaplan–Meier survival curves, univariate and multivariate Cox proportional hazard models to evaluate the association of rs633862 with overall survival (OS) in EOC patients. Results We found that rs633862 variant AG/GG genotypes were significantly associated with a longer OS by using univariate Cox proportional hazards regression analysis, compared with the rs633862 AA genotype (HR = 0.69, 95% CI [0.49–0.98], p = 0.035), albeit with a boardline significance in the multivariate analysis. Similar findings were observed in the subgroup of high-grade serous ovarian carcinoma. Further expression quantitative trait loci (eQTL) analysis indicated that the rs633862 AA genotype was associated with an increased level of ABO mRNA expression (p = 1.8 × 10−11). Conclusions Supplementary to the previous GWAS, our study provides additional evidence on the prognostic value of the 9q34.2 rs633862 variant in EOC patients, and this variant may function by regulating the ABO mRNA expression

Canakinumab in the treatment of systemic juvenile idiopathic arthritis: a retrospective single center study in China

ObjectiveSystemic juvenile idiopathic arthritis (sJIA) is characterized by excessive production of proinflammatory cytokines. As an anti-IL-1 agent, canakinumab has been approved in the USA and Europe for the treatment of sJIA patients aged ≥2 years. However, the use of canakinumab has never been reported in China. In this study, we aimed to assess the efficacy and safety of canakinumab in Chinese patients with sJIA.MethodsA total of 11 patients with sJIA who were treated with canakinumab were included in this study. Clinical data were collected retrospectively from medical records. Efficacy was evaluated by the systemic juvenile arthritis disease activity score (sJADAS). The follow-up was performed at canakinumab initiation, at months 1, 3, 6, 9 and 12, or at the last follow-up.ResultsOf the 11 patients enrolled, 91.0% (10/11) had previously received treatment with tocilizumab. The mean duration of canakinumab was 9 (3–18) months. 45.5% (5/11) of patients showed complete response, 45.5% (5/11) showed partial response, and 9.0% (1/11) showed no response. 18.2% (2/11) experienced disease flare during the treatment with canakinumab. 81.8% (9/11) of patients successfully reduced the dose of corticosteroids, with six discontinuing corticosteroids. 45.6% (5/11) of patients experienced infection. No serious adverse events occurred during the treatment with canakinumab.ConclusionsCanakinumab may be effective and tolerable for Chinese sJIA patients, helping to reduce the dosage of corticosteroids. However, additional researches on large samples are required to evaluate its efficacy and safety

Ribonucleic acid interference knockdown of IL-6 enhances the efficacy of cisplatin in laryngeal cancer stem cells by down-regulating the IL-6/STAT3/HIF1 pathway

Abstract Background Cisplatin has been used in the treatment of many cancers, including laryngeal cancer; however, its efficacy can be reduced due to the development of drug resistance. This study aimed to investigate whether interleukin-6 (IL-6) knockdown may enhance the efficacy of cisplatin in laryngeal cancer stem cells (CSC) and the potential involvement of the signal transducer and activator of transcription 3 (STAT3) and hypoxia-inducible factor 1 (HIF1) in this effect. Methods The ALDH+ and CD44+ CSC in Hep2 human laryngeal squamous cancer cells were identified by the fluorescence-activated cell sorting technique. IL-6, STAT3 and HIF1 mRNA and protein expressions were examined with quantitative real-time polymerase chain reaction and Western blot, respectively. Cell proliferation was measured by MTT assay. Tumorigenicity was measured by a colony formation assay and invasion was determined by a cell invasion assay. Apoptotic cells were counted by flow cytometry. Immunohistochemistry was performed to detect immunoreactive IL-6, STAT3 and HIF1 cells in xenografts. Results The mRNA and protein levels of IL-6, STAT3 and HIF1 were significantly increased in Hep2-CSC as compared with those from Hep2 cells. Application of siRNA-IL-6 to knockdown IL-6 resulted in significantly decreased IL-6, STAT3 and HIF1 mRNA and protein levels. IL-6 knockdown reduced cell proliferation, tumorigenicity and invasion and increased apoptosis within CSC. Enhanced degrees of suppression in these parameters were observed when IL-6 knockdown was combined with cisplatin in these CSC. Results from the xenograft study showed that the combination of IL-6 knockdown and cisplatin further inhibited the growth of xenografts as compared with that obtained in the cisplatin-injected group alone. Immunoreactive IL-6, STAT3 and HIF1 cell numbers were markedly reduced in IL-6 knockdown tumor tissues. IL-6, STAT3 and HIF1 immunoreactive cell counts were further reduced in tissue where IL-6 knockdown was combined with cisplatin treatment as compared with tissue receiving cisplatin alone. Conclusions IL-6 knockdown can increase chemo-drug efficacy of cisplatin, inhibit tumor growth and reduce the potential for tumor recurrence and metastasis in laryngeal cancer. The IL-6/STAT3/HIF1 pathway may represent an important target for investigating therapeutic strategies for the treatment of laryngeal cancer

Study on Water Purification Effect and Operation Parameters of Various Units of Wastewater Circulation

The discharge of wastewater from aquaculture ponds causes a certain degree of damage to the environment. It is necessary to continuously improve the treatment efficiency of wastewater treatment devices. The purpose of this study is to obtain an optimal ratio of wastewater circulation devices in order to obtain the best operating parameters and to reduce the discharge of polluted water. We constructed an experimental wastewater circulation device consisting of three units. The primary unit contained modified attapulgite (Al@TCAP-N), volcanic stone, and activated carbon for precipitation. The secondary and tertiary units used biological methods to enhance removal rates of nitrogen and phosphorus. Water quality indicators of total phosphorus (TP), total nitrogen (TN), ammonia (NH3-N), permanganate (CODMn), and total suspended solids (TSS) were detected. Water quality was tested under different matching ratios for three units of different hydraulic retention time (HRT) and load Results showed that the removal rate of TP, TN, NH3-N, and TSS reached 20–60%, 20%, 30–70%, and 10–80%, respectively. The average reduction efficiencies of secondary module chlorella and filler on TP, TN, NH3-N, CODMn, and TSS were 56.88%, 30.09%, 0.43%, 46.15%, and 53.70%, respectively. The best removal rate can be achieved when the matching ratio of each unit becomes 2:1:1 and the hydraulic retention time is maintained within 2 h in the high-concentration load. Finally, the average removal rates of TP, TN, NH3-N, and TSS reached 58.87%, 15.96%, 33.99%, and 28.89%, respectively. The second unit obtained the enhanced removal effect in this wastewater treatment system when adding microorganisms and activated sludge

Study on Water Purification Effect and Operation Parameters of Various Units of Wastewater Circulation

The discharge of wastewater from aquaculture ponds causes a certain degree of damage to the environment. It is necessary to continuously improve the treatment efficiency of wastewater treatment devices. The purpose of this study is to obtain an optimal ratio of wastewater circulation devices in order to obtain the best operating parameters and to reduce the discharge of polluted water. We constructed an experimental wastewater circulation device consisting of three units. The primary unit contained modified attapulgite (Al@TCAP-N), volcanic stone, and activated carbon for precipitation. The secondary and tertiary units used biological methods to enhance removal rates of nitrogen and phosphorus. Water quality indicators of total phosphorus (TP), total nitrogen (TN), ammonia (NH3-N), permanganate (CODMn), and total suspended solids (TSS) were detected. Water quality was tested under different matching ratios for three units of different hydraulic retention time (HRT) and load Results showed that the removal rate of TP, TN, NH3-N, and TSS reached 20–60%, 20%, 30–70%, and 10–80%, respectively. The average reduction efficiencies of secondary module chlorella and filler on TP, TN, NH3-N, CODMn, and TSS were 56.88%, 30.09%, 0.43%, 46.15%, and 53.70%, respectively. The best removal rate can be achieved when the matching ratio of each unit becomes 2:1:1 and the hydraulic retention time is maintained within 2 h in the high-concentration load. Finally, the average removal rates of TP, TN, NH3-N, and TSS reached 58.87%, 15.96%, 33.99%, and 28.89%, respectively. The second unit obtained the enhanced removal effect in this wastewater treatment system when adding microorganisms and activated sludge

Altered expression of transcription factors IRF4 and IRF8 in peripheral blood B cells is associated with clinical severity and circulating plasma cells frequency in patients with myasthenia gravis

<p>Previous studies have shown that interferon regulatory factor-4 (IRF4) and IRF8 play critical but distinct roles in the differentiation of B cells into plasma cells (PCs). In the present study, we aimed to measure the expression levels of IRF4 and IRF8 in B cells from patients with myasthenia gravis (MG) and to investigate whether the expression of IRF4 and IRF8 associates with pathogenesis of MG. A total of 35 anti-acetylcholine receptor (AChR) antibody (Ab)-positive patients with MG [20 generalized MG (GMG) and 15 ocular MG (OMG) and 25 healthy donors were recruited in this study. The quantitative myasthenia gravis score (QMGS) was used to evaluate the clinical severity. Real-time PCR and Western blot were used to measure the levels of IRF4 and IRF8 expressed in peripheral blood B cells. Peripheral blood CD138⁺ PCs were assayed by flow cytometry. Our data demonstrated that the mRNA/protein levels of IRF4 and IRF8 were significantly higher and lower, respectively, in patients with OMG/GMG groups compared with healthy controls. In addition, IRF4 expression was significantly higher and IRF8 expression was significantly lower in GMG group than in OMG group. Pearson’s correlation analysis revealed that IRF8 expression was negatively correlated with clinical severity, PCs frequency and anti-AChR Ab levels, while IRF4 expression and IRF4/IRF8 ratio was positively correlated with these parameters in two MG subgroups. Finally, glucocorticoid treatment can relieve the imbalance of IRF4/IRF8 in peripheral blood B cells, and this restoration is accompanied by reduced PCs frequency and clinical symptoms. These evidences suggest that IRF4 and IRF8 are important in the counter-balancing mechanisms controlling differentiation of PCs in MG. The disruption of the balanced IRF4/IFR8 ratio in B cells may play important roles in the pathogenesis of MG and offer a promising therapeutic target for the development of novel immunotherapy for MG patients.</p