Elevated Serum FGG Levels Prognosticate and Promote the Disease Progression in Prostate Cancer.

Castration-resistant prostate cancer (CRPC) threatens the health of men in general and no effective therapeutics currently exists for the treatment of CRPC. It is therefore of great importance to find a novel molecule that can be a biomarker and a therapeutic target for CRPC. First, we found that the serum fibrinogen gamma (FGG) levels in patients with CRPC were significantly higher than those with localized prostate cancer (PCa) through iTRAQ proteomics and ELISA experiments. Immunohistochemistry, quantitative real-time polymerase chain reaction and western blot also showed an increase of FGG expression in CRPC tissues and cells. Then we proved the proliferation, invasion and migration ability of CRPC cells were significantly reduced after FGG knockdown. The number of apoptotic cells increased at least sixfold after FGG silencing, and was observed in conjunction with an upregulation of p53, caspase 3, clea-caspase 3, and Bax, and a downregulation of Bcl2 and survivin. FGG knockdown in DU145 cells resulted in smaller xenografts than control cells in a mouse model. and we established that FGG is modulated by IL-6 which was increased in CRPC patients via phosphorylation of STAT3. The data suggests that FGG may be a potential therapeutic target and prognostic marker for CRPC.

CircDDX17 acts as a competing endogenous RNA for miR-605 in breast cancer progression.

OBJECTIVE: Circular RNAs (circRNAs), a novel class of noncoding RNAs, are reported to be involved in the progression of various cancers. CircDDX17 was reported as a tumour suppressor in colorectal cancer. However, the expression and role of circDDX17 in breast cancer remain unclear. PATIENTS AND METHODS: We used qPCR analysis to reveal the expression levels of circRNAs and miRNAs in breast cancer tissues and cell lines. The target relationship between circRNA and miRNAs was predicted using miRanda and then detected using a Luciferase reporter assay. The effects of circDDX17 and miR-605 on the growth of breast cancer were detected using MTT, colony formation assay and apoptosis analysis. RESULTS: In this study, low circDDX17 expression was observed in breast cancer tissues and cell lines. Moreover, circDDX17 expression was inversely associated with the clinicopathological parameters of tumour grade and advanced TNM stage (p<0.05). Functionally, overexpressed circDDX17 inhibited cell proliferation and colony formation and promoted cell apoptosis in breast cancer. Mechanistically, circDDX17 directly bound to miR-605, which functions as an oncogene in breast cancer, and its expression was associated with low overall survival of breast cancer patients. Finally, we found that circDDX17 suppressed cell proliferation by regulating cell cycle-related factors (CDK1 and p21), and the effect was reversed by miR-605 mimics. CONCLUSIONS: We identified the downregulation of circDDX17 in breast cancer, and circDDX17 acted as a tumour suppressor by inhibiting proliferation and promoting apoptosis through its function as a sponge of miR-605 in breast cancer, indicating that it serves as a potential biomarker and a therapeutic target for breast cancer.

[A retrospective study on combined modality therapy with or without surgery for advanced hypopharyngeal squamous cell carcinoma: an analysis of 119 cases].

Objective: To compare the treatment outcomes for locally advanced hypopharyngeal carcinoma between surgery plus radio(chemo) therapy(SRT) and non-surgery chemoradiotherapy(CRT). Methods: A total of 119 patients diagnosed with advanced hypopharyngeal carcinoma without distant metastases between 2010 and 2014 were identified in the Chinese People's Liberation Army General Hospital, and they were divided into 2 groups: 42 cases in SRT group and 77 cases in CRT group. Patients' clinical information was collected. Survival rates and prognostic factors were analyzed by the Kaplan-Meier method with SPSS 23.0 software. The survival rates, laryngeal preservation rates and complication rates were compared between the two groups using the chi-square test.Among the 119 patients, 112 were males and 7 were females. Age ranged from 27 to 78 years, with an average age of 57 years. Results: There were no significant difference between the SRT and CRT group for five-year disease-free survival (DFS, 53.9% vs. 45.1%, χ(2)=1.251, P=0.263) and overall survival (OS, 54.9% vs. 45.6%, χ(2)=1.749, P=0.186). Compared to SRT group, CRT group did not showed the significant increase of treatment complications (χ(2)=0.858, P=0.354), with a higher laryngeal preservation rate (50.0% vs. 71.4%, χ(2)=6.493, P=0.011). Conclusions: Advanced hypopharyngeal carcinoma is of high malignancy and poor prognosis. Combined modality treatment is a main approach for advanced hypopharyngeal cancer. SRT offers disease-free survival and overall survival rates equivalent to CRT, but with a higher laryngeal preservation rate.

The impact of a novel transendometrial approach for caesarean myomectomy on obstetric outcomes of subsequent pregnancy: a longitudinal panel study.

OBJECTIVE: To evaluate the obstetric and surgical outcomes of a novel transendometrial approach for myomectomy during caesarean section in subsequent pregnancies. DESIGN: Longitudinal panel study. SETTING: Chang Gung Memorial Hospital, Taiwan, with approximately 5000 births per annum. POPULATION: Pregnant women complicated with uterine myoma. METHOD: Sixty-three pregnant women who received transendometrial myomectomy during the first caesarean delivery reported a subsequent live pregnancy and planned an elective repeat caesarean delivery. MAIN OUTCOME MEASURES: Obstetric outcomes consisted of gestational age at birth, newborn weight, Apgar score, birthweight adequacy, uterine rupture, placental abruption, placenta praevia, placenta accreta, spontaneous preterm birth and preterm premature rupture of membranes. Surgical outcomes consisted of surgical time, blood loss, blood transfusion, postoperative fever, length of hospital stay and mean adhesion score. RESULT: The mean gestational age at birth and newborn weight at the subsequent caesarean section were superior to those at the first caesarean delivery. Spontaneous preterm birth, small-for-gestational-age infants and preterm premature rupture of membranes occurred more often in the first pregnancy than in the subsequent pregnancy. The mean surgical time was shorter for the subsequent caesarean delivery than for the first caesarean delivery combined with myomectomy. The other surgical composite outcomes of blood loss, blood transfusion, postoperative fever, length of hospital stay and mean adhesion score were similar across the two stages of caesarean deliveries. CONCLUSION: The novel transendometrial approach for caesarean myomectomy may improve the obstetric outcomes of subsequent pregnancy without causing any additional immediate and long-term adverse surgical outcomes. TWEETABLE ABSTRACT: Transendometrial caesarean myomectomy may improve future obstetric outcomes.

JNK-deficiency enhanced oncolytic vaccinia virus replication and blocked activation of double-stranded RNA-dependent protein kinase.

Vaccinia virus has recently been used as an expression vector for gene delivery and an oncolytic agent for cancer therapy. Although it has been established that interferon-induced double-stranded RNA (dsRNA)-activated protein kinase (PKR) and RNase L interfere with viral replication, little else is known about the other host factors that might affect viral replication and virus-mediated host cell killing. In this study, we evaluated the roles of c-Jun NH2-terminal kinase (JNK) in oncolytic vaccinia virus replication and vaccinia virus-mediated host cell killing. We found that JNK knockout mouse embryonic fibroblasts (MEFs) were more susceptible to oncolytic vaccinia virus infection than wild-type MEFs. Moreover, viral replication and the production of infectious viral progeny were up to 100-fold greater in JNK-deficient MEFs than in wild-type MEFs. A similar result was observed for wild-type vaccinia virus. The increased killing of infected cells and the production of viral progeny was also observed in wild-type MEFs that had been treated with JNK inhibitors and in human colon cancer cells that had been transfected with dominant-negative JNK constructs. Moreover, testing on several human lung cancer cell lines and HeLa cells showed an inverse correlation between levels of JNK expression and susceptibility to oncolytic vaccinia virus. Our study also revealed that oncolytic virus infection-mediated PKR activation was blocked or diminished in JNK-deficient MEFs. The adenovirus-mediated ectopic expression of human PKR in JNK-deficient MEFs reduced vaccinia virus replication to the levels observed in wild-type MEFs, indicating that JNK is required for vaccinia virus to efficiently activate PKR. Our results demonstrated that the cellular status of JNK function can dramatically affect oncolytic vaccinia virus replication and vaccinia virus-mediated host cell killing. This finding may enable further improvements in oncolytic virotherapy using vaccinia virus.

Isolation, characterization and identification of lactic acid bacteria and yeasts from sour Mifen, a traditional fermented rice noodle from China.

AIMS: Considering the effect of natural fermentation on the textural improvement of fermented rice noodles in China and South Asia, and given the lack of reports concerning microbial populations and structure in the fermentation process, this study aims to determine the number of viable micro-organisms and identify the species isolated from the local factories, and to assess their potential use as a starter culture from their enzymatic profiles. METHODS AND RESULTS: Fourteen samples from three local factories were analysed for the presence of micro-organisms. A total of 170 lactic acid bacteria (LAB) and 96 yeasts were isolated from the factories. The isolates were phenotypically characterized by using API 50 CHL kits, API 20 Strep kits, API ID 32 C kits and by performing additional biochemical tests. The enzymatic profiles of isolates were assessed by using API ZYM kits. Lactobacillus plantarum and Saccharomyces cerevisiae were identified as predominant species in the fermented supernatants. A majority of the isolates of LAB and yeasts displayed activities of alpha-glucosidase, beta-glucosidase, lipase and trypsin. CONCLUSIONS: The microbial composition and strain characteristics present in the fermentation supernatant demonstrate that a majority of micro-organisms have the ability to digest starch, sugar, protein or lipid. It supports our previous work in which the rice starch was modified and purified by fermentation and thus improves the texture of rice noodles. SIGNIFICANCE AND IMPACT OF THE STUDY: The dominant strains would be important in developing a starter culture. The results can form the basis for the improvement of product quality and consistency.

A recurrent intragenic genomic duplication, other novel mutations in NLRP7 and imprinting defects in recurrent biparental hydatidiform moles.

A complete hydatidiform mole (CHM) is an abnormal pregnancy with hyperproliferative vesicular trophoblast and no fetal development. Most CHM are sporadic and androgenetic, but recurrent HM have biparental inheritance (BiHM) with disrupted DNA methylation at differentially methylated regions (DMRs) of imprinted loci. Some women with recurrent BiHM have mutations in the NLRP7 gene on chromosome 19q13.42. Using bisulfite genomic sequencing at eight imprinted DMRs on DNA from two BiHMs, we found a pattern of failure to acquire or maintain DNA methylation at DMRs (PEG3, SNRPN, KCNQ1OT1, GNAS exon 1A) that normally acquire CpG methylation during oogenesis, but not at H19, which acquires CpG methylation during spermatogenesis. Secondary imprints at the GNAS locus showed variable abnormal patterns with both gain and loss of CpG methylation. We found novel missense and splice-site mutations in NLRP7 in women with non-familial recurrent BiHM. We identified and characterized a homozygous intragenic tandem duplication including exons 2 through 5 of NLRP7 that results in a predicted truncated protein in affected women of three unrelated Egyptian kindreds, suggesting a founder effect. Our findings firmly establish that NLRP7 mutations are a major cause of BiHM and confirm presence of a complex pattern of imprinting abnormalities in BiHM tissues.

Evaluation of the cytotoxicity, mutagenicity and antimutagenicity of emerging edible plants.

This study evaluates the toxic, mutagenic and antimutagenic effects of emerging edible plants that are consumed as new leafy vegetables in Taiwan. Among eight plant extracts, only the extracts of Sol (Solanum nigrum L.) showed cytotoxicity to Salmonella typhimurium TA100 in the absence of S9 mix. The toxicity of extracts from different parts of the Sol plant, such as leaf and stem, immature fruit and mature fruit, towards S. typhimurium TA100 and human lymphocytes was also assayed. The immature fruit extracts of Sol exhibited strong cytotoxicity with dose dependence and induced significant DNA damage in human lymphocytes based on the comet assay. However, no mutagenicity was found in eight plant extracts to TA98 or TA100 either with or without the S9 mixture. Sol and Sec [Sechium edule (Jacq.) Swartz] extracts showed the strongest inhibitory effect towards the mutagenicity of 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ) in S. typhimurium TA98 and TA100; the ID(50) was less then 1 mg/plate. Cra [Crassocephalum creidioides (Benth.) S. Moore] extracts also expressed moderate antimutagenic activities towards IQ and benzo[a]pyrene (B[a]P) either in TA98 or in TA100; the ID(50) was 1.63-2.41 mg/plate. The extracts from Bas (Basella alba L.), Bou (Boussingaultia gracilis Miers var. pseudobaselloides Bailey), Cen (Centella asiatica L. Urban), Cor (Corchorus olitorius L.) and Por (Portulaca oleracea L.) showed weak to moderate inhibition of mutagenicity of IQ. However, the potential antimutagenicity of these plant extracts towards B[a]P was weaker than that towards IQ. For a direct mutagen, 4-nitroquinoline-N-oxide (NQNO), only the Sol extracts showed strong inhibitory effects in the TA100 system. The antimutagenic activity of water extracts of Sec was partly reduced by heating at 100 degrees C for 20 min. The heat-stable antimutagens in Sec extracts could be produced in the plant extract preparation process. Fractions with molecular weights above 30,000 showed the strongest antimutagenicity and peroxidase activity in all the fractions of the Sec extracts.

An in vitro monitoring system for simulated thermal process in cryosurgery.

This paper describes a new in vitro experimental model that records temperature changes over a culture plate, which then can be used to assess the biological effects of cryosurgery. A cryoprobe and 16 thermocouples set up by a computer control system were used to monitor the temperature changes during freezing and thawing in a culture plate, and the data were used to create a temperature profile of the entire plate. Location of the thermocouples was confirmed by a digital camera viewing from under the plate, and temperature changes at any point in the interpolated areas were estimated using a curve fitting method. The estimated temperature was checked by sampling with four additional randomly placed thermocouples. Linear regression analysis showed that the estimated temperature and measured temperature were very close (correlation coefficients 0.98-0.99). MBT-2 tumor cells were cultured and then subjected to simulated cryosurgery. The surviving cells were stained with crystal violet and the cell death boundary was detected by image processing. Temperature history at the cell death boundary was retrieved and analyzed. With this system it is possible to recreate the temperature changes that result in a certain biological effect (such as cell death) during the process of simulated cryosurgery.