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Purpose: The interferon regulatory factor 2 (IRF-2) acted as a tumor suppressor. We inspected IRF-2 as a predictor of prognosis in gastric cancer (GC) patients and tried to find out the potential molecular mechanism.Methods: In this study, the association between IRF-2 expression and clinical or prognosis significance was investigated in 86 pairs of tumor and the adjacent normal gastric tissues from GC patients. After establishing the stable cell lines, the Transwell assays were deduced to evaluate the malignancy of tumor. Then, microarray assay was carried out and the GO/KEGG pathway analyses were conducted to identify IRF-2's target gene. The relationship between IRF-2 and matrix metalloproteinases 1 (MMP-1) was also investigated by the immunohistochemistry in 15 pairs of tumor and adjacent normal gastric tissues.Results: We found that IRF-2 expression level in GC was significantly correlated with the prognosis of the patients. Transwell assays suggested an impaired ability of invasion and migration in IRF-2-overexpressed GC cells and a progressive malignant phenotype in IRF-2-knockdown GC cells. Ninety differentially expressed genes were found between IRF-2-overexpressed GC cells and its normal control sets by microarray. We demonstrated that MMP-1 was canonical in the network of differentially expressed genes by GO and KEGG pathway analysis and its expression level was markedly decreased in IRF-2-overexpressed cells of MKN-45 and increased in IRF-2-knockdown cells of SGC-7901. The expression of MMP-1 was inversely correlated with IRF-2 in GAC TMA specimens.Conclusion: IRF-2 may inhibit GC progression by down-regulating MMP-1 level. [ABSTRACT FROM AUTHOR]

In order to identify the factors that could predict the efficacy of exclusive enteral nutrition (EEN) in inducing remission of active CD. Baseline clinical and laboratory covariates were correlated with the outcome (clinical remission) of EEN in active CD (CDAI ≥150) by both univariable and multivariable analyses. A total of 67 from a consecutive of 136 active CD patients were enrolled. L4b (from treitz ligament to distal 1/3 ileum) involvement was negatively and high serum albumin (≥35 g/L) was positively associated with clinical remission (OR: 0.14, OR: 14.71). In conclusion, L4b sparing and high serum albumin might predict a favorable outcome of EEN in active CD (ClinicalTrials.gov ID: NCT 02942511). [ABSTRACT FROM AUTHOR]

Background: As a potential tumor suppressor gene, Claudin-7 (Cldn7), which is a component of tight junctions, may play an important role in colorectal cancer occurrence and development.Aims: To generate a knockout mouse model of inducible conditional Cldn7 in the intestine and analyze the phenotype of the mice after induction with tamoxifen.Methods: We constructed Cldn7-flox transgenic mice and crossed them with Villin-CreERT2 mice. The Cldn7 inducible conditional knockout mice appeared normal and were well developed at birth. We induced Cldn7 gene deletion by injecting different dosages of tamoxifen into the mice and then conducted a further phenotypic analysis.Results: After induction for 5 days in succession at a dose of 200 µl tamoxifen in sunflower oil at 10 mg/ml per mouse every time, the mice appeared dehydrated, had a lower temperature, and displayed inactivity or death. The results of hematoxylin-eosin staining showed that the intestines of the Cldn7 inducible conditional knockout mice had severe intestinal defects that included epithelial cell sloughing, necrosis, inflammation and hyperplasia. Owing to the death of ICKO mice, we adjusted the dose of tamoxifen to a dose of 100 µl in sunflower oil at 10 mg/ml per mouse (aged more than 8 weeks old) every 4 days. And we could induce atypical hyperplasia and adenoma in the intestine. Immunofluorescent staining indicated that the intestinal epithelial structure was destroyed. Electron microscopy experimental analysis indicated that the intercellular gap along the basolateral membrane of Cldn7 inducible conditional knockout mice in the intestine was increased and that contact between the cells and matrix was loosened.Conclusions: We generated a model of intestinal Cldn7 inducible conditional knockout mice. Intestinal Cldn7 deletion induced by tamoxifen initiated inflammation and hyperplasia in mice. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the potential of various metrics derived from mono-exponential model (MEM), bi-exponential model (BEM) and stretched exponential model (SEM)-based diffusion-weighted imaging (DWI) in diagnosing and differentiating the pathological subtypes and grades of uterine cervical carcinoma.Methods: 71 newly diagnosed patients with cervical carcinoma (50 cases of squamous cell carcinoma [SCC] and 21 cases of adenocarcinoma [AC]) and 32 healthy volunteers received DWI with multiple b values. The apparent diffusion coefficient (ADC), pure molecular diffusion (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), water molecular diffusion heterogeneity index (alpha), and distributed diffusion coefficient (DDC) were calculated and compared between tumour and normal cervix, among different pathological subtypes and grades.Results: All of the parameters were significantly lower in cervical carcinoma than normal cervical stroma except alpha. SCC showed lower ADC, D, f and DDC values and higher D* value than AC; D and DDC values of SCC and ADC and D values of AC were lower in the poorly differentiated group than those in the well-moderately differentiated group.Conclusion: Compared with MEM, diffusion parameters from BEM and SEM may offer additional information in cervical carcinoma diagnosis, predicting pathological tumour subtypes and grades, while f and D showed promising significance.Key Points: • DWI-derived parameters by different models are related but provide diversified information. • Commonly used ADC by MEM of DWI overestimates the tissue water diffusivity. • DWI processed by BEM could separate blood perfusion from true diffusion effects. • The derived diffusion-related and perfusion-related parameters by BEM are superior to ADC. [ABSTRACT FROM AUTHOR]

Introduction: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA), and is being investigated for the treatment of psoriasis. Both conditions can present in women of child-bearing potential, but pregnancy was an exclusion and discontinuation criterion in tofacitinib randomized controlled trials (RCTs) because of the unknown effects of tofacitinib on mother and child. Tofacitinib is a small molecule that has the potential to cross the placenta.Objective: The objective was to report outcomes of pregnancy cases identified through April 2014 from tofacitinib RA/psoriasis RCTs, RA post-approval non-interventional studies, and spontaneous adverse-event reporting.Methods: Pregnancy outcomes were categorized as follows: healthy newborn, medical termination, fetal death, congenital malformation, spontaneous abortion, or pending/lost to follow-up.Results: Out of 9815 patients, 1821 female patients of child-bearing age were enrolled in the RA/psoriasis RCTs; 47 women became pregnant, including 33 who received tofacitinib monotherapy, 13 who received combination therapy with methotrexate (RA patients only), and one patient whose therapy was still blinded. No fetal deaths were reported. One congenital pulmonary valve stenosis (monotherapy, n = 1), seven spontaneous abortions (monotherapy, n = 4; combination therapy, n = 3), and eight medical terminations (monotherapy, n = 4; combination therapy, n = 3; blinded therapy, n = 1) were identified. Remaining cases reported healthy newborns (n = 25) or were pending/lost to follow-up (n = 6). Forty-four cases of paternal exposure to tofacitinib were reported (monotherapy, n = 43; combination therapy, n = 1), including five spontaneous abortions (monotherapy, n = 4; combination therapy, n = 1), 23 healthy newborns, and 16 pending/lost to follow-up.Conclusions: The pregnancy outcomes reported in this small number of RA/psoriasis patients appear similar to those observed in the general population and in patients treated with biologic therapies for inflammatory diseases. However, definitive conclusions cannot be drawn, and pregnancy outcomes in patients receiving tofacitinib will continue to be monitored. [ABSTRACT FROM AUTHOR]

To investigate the anti-cancer effects and molecular mechanism of deguelin on the human leukemia HL-60 cells, to explore the expression and clinical significance of p-AKT, survivin and Bcl-2 in leukemia cell line HL-60 cell. Cell growth rate was assessed by MTT assay. Apoptotic index was evaluated by TUNEL staining. Apoptosis was detected by Annexin V-FITC Apoptosis Detection Kit and transmission electron microscopy (TEM), expression of p-Akt, Bcl-2 and surviving in HL-60 cells was checked by Western blot. Deguelin presented striking proliferation inhibition potency on HL-60 cells in vitro, with the I(C50) value for 48 h being 20.14 nM, and induced apoptosis in HL-60 in a concentration-time-dependent manner. Apoptotic bodies and cell shrinkage and fragmentation were observed by TUNEL and TEM. Deguelin-induced cells morphological changes and degraded several kinase proteins, including Bcl-2 and survivin (members of lap). The degradation of these kinases blocked PI3K/Akt survival signal pathways, inducing apoptosis. Deguelin may induce HL-60 cell apoptosis through depletion of multiple kinase proteins and blockage of survival signal pathways of HL-60 cells. [ABSTRACT FROM AUTHOR]

Acute lymphoblastic leukemia (ALL) accounts for 20-30% of adult leukemia in the West. However, detailed studies of B-cell-specific ALL in adult Asian populations are lacking. We diagnosed and characterized 137 consecutive cases of precursor B lymphoblastic leukemia (precursor B-cell ALL) presented to our laboratory in Shanghai using the WHO 2001 classification system. Patient clinical, phenotypic and cytogenetic characteristics were correlated with outcome. In contrast to Western studies, females (71) outnumbered males (66) partly due to an increased prevalence of the CD10- pro B-cell phenotype. Females with a CD10- pro B-cell phenotype exhibited significantly better overall survival than males. The most common cytogenetic abnormality was the Philadelphia chromosome (PH/BCR/ABL) which was found in approximately 37% of the cases. Cases of precursor B cell ALL lacking the PH/BCR/ABL genotype exhibited a pronounced age-dependent, gender prevalence with a modal age in the sixth decade for females compared to the second decade for males. These findings suggest significant geographic heterogeneity in precursor B-cell ALL which may be of both etiological and therapeutic significance. [ABSTRACT FROM AUTHOR]

We have investigated the effects of temperature on the conductance and voltage-dependent kinetics of cardiac gap junction channels between pairs of seven-day embryonic chick ventricle myocytes over the range of 14-26 degrees C. Records of junctional conductance (Gj) and steady-state unit junctional channel activity were made using the whole-cell double patch-clamp technique while the bath temperature was steadily changed at a rate of about 4 degrees C/min. The decrease in Gj upon cooling was biphasic with a distinct break at 21 degrees C. In 12 cell pairs, Q10 was 2.2 from 26 to 21 degrees C, while between 21 and 14 degrees C it was 6.5. The mean Gj at 22 degrees C (Gj22) was 3.0 +/- 2.1 nS, ranging in different preparations from 0.24 to 6.4 nS. At room temperature, embryonic cardiac gap junctions contain channels with conductance states near 240, 200, 160, 120, 80 and 40 pS. In the present study, we demonstrate that cooling decreases the frequency of channel openings at all conductance levels, and at temperatures below 20 degrees C shifts the prevalence of openings from higher to lower conductance states: all 240 pS openings disappear below 20 degrees C; 200 pS openings are suppressed at 17 degrees C; below 16 degrees C 160 and 120 pS events disappear and only 80 and 40 pS states are seen. Temperature also affected the voltage-dependent kinetics of the channels. Application of a 6 sec, 80 mV voltage step across the junction (Vj80) caused a biexponential decay in junctional conductance. Decay was faster at lower temperatures, whereas the rate of recovery of Gj after returning to Vj0 was slowed. Cooling reduced the fast decay time constant, increased both recovery time constants, and decreased the magnitude of Gj decay, thus leaving a 10-16% larger residual conductance (Gss/Ginit, +/- 80 mV Vj) at 18 than at 22 degrees C. From these results we propose that embryonic chick cardiac gap junctions contain at least two classes of channels with different conductances and temperature sensitivities. [ABSTRACT FROM AUTHOR]