PCDH10 inhibits invasion of lymphoma cells by regulating ß-catenin.

OBJECTIVE: The aim of this study was to investigate the effect of protocadherin 10 (PCDH10) on the invasive potential of lymphoma cells by regulating matrix metalloproteinase-7 (MMP7) and MMP9 via targeting ß-catenin. MATERIALS AND METHODS: The mRNA and protein expressions of PCDH10, ß-catenin, MMP7 and MMP9 in lymphoma cell lines were examined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot, respectively. Raji cells with low expression of PCDH10 were transiently transfected with pCMV5-HA-PCDH10 or pcDNA5-His-ß-catenin. Meanwhile, HUT-78 cells with high expression of PCDH10 were transfected with PCDH10-shRNA or ß-catenin-shRNA. Subsequently, the expression levels of ß-catenin, MMP7 and MMP9 in transfected lymphoma cells were determined as well. In addition, the regulatory effects of PCDH10 on the invasive potential of lymphoma cells were explored by transwell assay. RESULTS: PCDH10 expression was negatively correlated with the expressions of ß-catenin, MMP7 and MMP9 in several lymphoma cell lines. Transfection of HA-PCDH10 in human-derived malignant B lymphoma cell line Raji markedly down-regulated the protein levels of ß-catenin, MMP7 and MMP9. However, the mRNA level of ß-catenin was not influenced by PCDH10. Interference with PCDH10 in HUT-78 cells with high expression of PCDH10 significantly increased the protein expressions of ß-catenin, MMP7, and MMP9. However, no significant changes were observed in the mRNA expression of ß-catenin. In addition, knockdown of ß-catenin in cells with high expression of PCDH10 remarkably down-regulated the expression levels of MMP7 and MMP9. CONCLUSIONS: PCDH10 overexpression in lymphoma cells downregulates ß-catenin expression, as well as inhibits the expressions of MMP7 and MMP9, eventually inhibiting the invasive potential of lymphoma cells.

[Combined detection of KRAS, NRAS, BRAF and PIK3CA mutations in the plasma and tumor tissues of colorectal cancer patients].

Objective: To analyze the concordance of KRAS, NRAS, BRAF and PIK3CA gene mutations detected in plasma and matched tumor tissues in colorectal cancer patients, in order to provide good evidences to support plasma could be a potential surrogate of tumor tissue for gene mutation test. Methods: One hundred and seventy-five cases of colorectal cancer were collected at the First Hospital of Jilin University, from October 2016 to October 2017.There were 101 males and 74 females, their ages ranged from 28 to 85 years,with median age of 59 years. The KRAS, NRAS, BRAF and PIK3CA gene mutations in the plasma and paired tumor specimens of all patients were detected by next generation sequencing. Results: The results of tissue samples test were gold standard. Comparison of the four genes showed that concordance rates between plasma and tissue samples were 81.1%(Kappa=0.543), 99.4%(Kappa=0.886), 99.4% (Kappa=0.886) and 97.7%(Kappa=0.714) respectively for KRAS, NRAS, BRAF and PIK3CA. The plasma detection rates of these genes were related to tumor stage(P=0.001), but not to gender(P=0.468) and age(P=1.000) of patients. Conclusions: The study shows a high concordance of KRAS, NRAS, BRAF and PIK3CA gene mutations in plasma against mutation status in tumor tissue. In colorectal cancer, tumor tissue remains the best specimen for gene detection. However, patients from tumor tissue specimens cannot be obtained, especially those with advanced metastases, plasma can be used instead of tissue to detect the mutation status of KRAS, NRAS, BRAF and PIK3CA to guide targeted therapy.

[The study of nomogram based on Ishak inflammation score for recurrence of hepatocellular carcinoma after curative resection].

Objective: To investigate the correlation between Ishak inflammation score and the clinicopathological characteristics and recurrence of patients with hepatocellular carcinoma (HCC) after curative resection, and then set up a recurrence nomogram for HCC. Methods: A total of 326 patients with HCC after curative resection from January 2006 to December 2009 were studied retrospectively as training cohort and 110 HCC patients after surgery from January 2010 to December 2012 were used as validation cohort.Clinical follow-up data and peritumoral Ishak inflammation score in training cohort were used to set up a nomogram predicting recurrence of HCC, which was verified by validation cohort. Kaplan-Meier and Cox proportional hazard regression model were used to analyzed accuracy of model prediction. Results: According to Ishak inflammation score, patients were divided into four subgroups: Grade Ⅰ(1-4 scores), Grade Ⅱ(5-8 scores), Grade Ⅲ (9-12 scores) and Grade Ⅳ(13-18 scores). Ishak inflammation score were associated with aspartate transaminase(median 36.0 U/L, P=0.011), γ-glutamyl transpeptidase(median 54.5 U/L, P=0.005), HBV-DNA load(20.5%>10(6) copies/ml, P=0.015) and microvascular invasion(26.7% positive, P=0.021). Multivariate analysis showed that Ishak inflammation score(P=0.007), HBV-DNA load(P<0.01), tumor size(P=0.001) and microvascular invasion(P=0.001) were related with the recurrence of HCC patients.These four risk factors were incorporated into the nomogram.Calibration curves of the nomogram had good agreement between prediction and observation in the probability of recurrence.Both C-indexes and receiver operating characteristic curve analyses revealed that this nomogram had better predictive abilities than those of the AJCC and Barcelona Clinic Liver Cancer (BCLC) stage systems.These results were verified by the validation cohort. Conclusion: A nomogram based on Ishak inflammation score could accurately predict the recurrence of HCC and contribute to HCC relapse surveillance after curative hepatectomy.

Changes in hematological parameters in α-thalassemia individuals co-inherited with erythroid Krüppel-like factor mutations.

Phenotypic variations in α-thalassemia mainly depend on the defective α-globin gene number. Genetic modifiers of the phenotype of Hemoglobin H (HbH) disease were poorly reported, apart from ß-thalassemia allele that was identified ameliorating the severity of α-thalassemia. Because erythroid Krüppel-like factor (KLF1) mutations can modulate the red blood phenotype, we evaluated its effect on the α-thalassemia phenotype. Overall, we identified 72 subjects with five different KLF1 heterozygous mutations in 1468 individuals, including 65 out of 432 α-thalassemia carriers with fetal hemoglobin (HbF) levels ≥1%, 0 out of 310 carriers with HbF levels <1% and 7 out of 726 HbH disease patients. We firstly established the link between KLF1 mutations and relatively elevated hemoglobin A2 (HbA2 ) and HbF levels, along with lower mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) values in a group of α-thalassemia carriers. However, we concluded that KLF1 mutations were not significantly linked to HbH disease severity. On the basis of HBA or HBB genotype and gender, clinical severity of patients with HbH disease was correctly predicted in 73.3% cases. It may improve the screening and diagnostic assessment of α-thalassemia.

A unique surface-initiated property of nanoparticles and application for the synthesis of hybrid organic-inorganic nanoparticles.

We report a unique property of nanoparticles to initiate acrylic acid and acrylamide solution polymerization under low air pressure conditions. This property could be applied to synthesize a wide variety of hybrid organic-inorganic nanoparticles, which hold great promise for use in nanophotonics, catalysis, and medical applications.

Synergistic effects of cyclic strain and Th1-like cytokines on tenascin-C production by rheumatic aortic valve interstitial cells.

Tenascin-C (TN-C) is a key component of extracellular matrix (ECM) and its expression process is poorly understood during rheumatic heart valvular disease (RHVD). In this study, we found that interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha and TN-C concentrations in patients with RHVD were significantly higher than in normal controls. More IFN-gamma receptors and TNF receptors were found being expressed on rheumatic aortic valves interstitial cells than on non-rheumatic ones and their expression was patients' sera dependent. Antibodies neutralizing IFN-gamma or TNF-alpha could attenuate patients' sera-induced TN-C transcription by isolated rheumatic aortic valves interstitial cells. By application with different protein kinase inhibitors, we found that combined with cyclic strain, TNF-alpha and IFN-gamma induced TN-C transcription through the RhoA/ROCK signalling pathway. At the same time, p38 mitogen-activated protein kinase was involved in TNF-alpha and IFN-gamma induced TN-C transcription. TNF-alpha also increased TN-C mRNA level by additional PKC and ERK 1/2 activation. Our finding revealed a new insight into ECM remodelling during RHVD pathogenesis and new mechanisms involved in the clinical anti-IFN-gamma and anti-TNF-alpha therapy.