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Objective To compare the effects of different doses of normal saline, irrigation durations and intervals of conjunctival sac irrigation before intraocular surgery in order to provide evidence for preparation of emergency intraocular surgery. Methods A total of 126 patients admitted to our ophthalmology department from September 2016 to May 2017 were recruited in this study. The patients were randomly divided into 3 groups, with 42 cases in each group, and were given conjunctival sac irrigation once with 5, 15, and 30 mL normal saline before the operation. The positive rate of bacterial culture, conjunctival congestion, corneal damage, and incidence of infectious endophthalmitis in 2 weeks after the operation were observed. Then based on the above dose results, 126 volunteers were subjected as study groups for different intervals. These participants were randomly assigned into 3 groups (n=42) cases, and were given conjunctival sac irrigation with normal saline for 3 times at intervals of 0.5, 1.0 and 1.5 h, respectively. The positive rate of bacterial culture and tear film rupture time after irrigation were observed. Results In different dose groups, there were no significant differences in the positive rate of bacteria and conjunctival congestion rate (P < 0.05). The 30 mL group had obviously higher conjunctival congestion rate than the 5 mL group (30.95% vs 9.52%, P < 0.05). No infectious endophthalmitis occurred in the 3 groups. The positive rate of bacteria was significantly reduced in different irrigation times and intervals after 3 rinses (P < 0.05). After irrigation for the first time, the positive rate was remarkably lower in the 0.5 and 1.0 h interval groups than the 1.5 h group (P < 0.05). After 3 times of irrigation, the tear film rupture time was statistically shorter in the 0.5 h group than the other 2 groups (P < 0.05), and no difference was seen between the latter 2 groups. Conclusion Conjunctival sac irrigation with 5 to 30 mL normal saline reduces the bacterial positive rate, and potential infection. The conjunctival irritation can be significantly reduced by as low as 5 mL normal saline. Irrigation for over 3 times, with low dose (5 mL) in 1.0 h before operation can obviously reduce the bacteria of conjunctival sac and tear film injury, and provide a safe microenvironment of conjunctival sac for emergency intraocular surgery. more...

BackgroundMetastatic relapse of prostate cancer after radiotherapy is a significant cause of prostate cancer-related morbidity and mortality. PLOD2 is a mediator of invasion and metastasis that we identified as being upregulated in our highly aggressive radiorecurrent prostate cancer cell line.MethodsPatient dataset analysis was conducted using a variety of prostate cancer cohorts. Prostate cancer cell lines were treated with siRNA, or the drug PX-478 prior to in vitro invasion, migration, or in vivo chick embryo (CAM) extravasation assay. Protein levels were detected by western blot. For RNA analysis, RNA sequencing was conducted on PLOD2 knockdown cells and validated by qRT-PCR.ResultsPLOD2 is a negative prognostic factor associated with biochemical relapse, driving invasion, migration, and extravasation in radiorecurrent prostate cancer. Mechanistically, HIF1α upregulation drives PLOD2 expression in our radiorecurrent prostate cancer cells, which is effectively inhibited by HIF1α inhibitor PX-478 to reduce invasion, migration, and extravasation. Finally, the long non-coding RNA LNCSRLR acts as a promoter of invasion downstream of PLOD2.ConclusionsTogether, our results demonstrate for the first time the role of PLOD2 in radiorecurrent prostate cancer invasiveness, and point towards its potential as a therapeutic target to reduce metastasis and improve survival outcomes in prostate cancer patients. more...

To model the problem of radiation resistance in prostate cancer, cell lines mimicking a clinical course of conventionally fractionated or hypofractionated radiotherapy have been generated. Proteomic analysis of radiation resistant and radiosensitive DU145 prostate cancer cells detected 4410 proteins. Over 400 proteins were differentially expressed across both radiation resistant cell lines and pathway analysis revealed enrichment in epithelial to mesenchymal transition, glycolysis and hypoxia. From the radiation resistant protein candidates, the cell surface protein CD44 was identified in the glycolysis and epithelial to mesenchymal transition pathways and may serve as a potential therapeutic target. more...

Abstract Background The HOX11/TLX1 (hereafter referred to as HOX11) homeobox gene was originally identified at a t(10;14)(q24;q11) translocation breakpoint, a chromosomal abnormality observed in 5-7% of T cell acute lymphoblastic leukemias (T-ALLs). We previously reported a predisposition to aberrant spindle assembly checkpoint arrest and heightened incidences of chromosome missegregation in HOX11-overexpressing B lymphocytes following exposure to spindle poisons. The purpose of the current study was to evaluate cell cycle specific expression of HOX11. Results Cell cycle specific expression studies revealed a phosphorylated form of HOX11 detectable only in the mitotic fraction of cells after treatment with inhibitors to arrest cells at different stages of the cell cycle. Mutational analyses revealed phosphorylation on threonine-247 (Thr247), a conserved amino acid that defines the HOX11 gene family and is integral for the association with DNA binding elements. The effect of HOX11 phosphorylation on its ability to modulate expression of the downstream target, cyclin B1, was tested. A HOX11 mutant in which Thr247 was substituted with glutamic acid (HOX11 T247E), thereby mimicking a constitutively phosphorylated HOX11 isoform, was unable to bind the cyclin B1 promoter or enhance levels of the cyclin B1 protein. Expression of the wildtype HOX11 was associated with accelerated progression through the G2/M phase of the cell cycle, impaired synchronization in prometaphase and reduced apoptosis whereas expression of the HOX11 T247E mutant restored cell cycle kinetics, the spindle checkpoint and apoptosis. Conclusions Our results demonstrate that the transcriptional activity of HOX11 is regulated by phosphorylation of Thr247 in a cell cycle-specific manner and that this phosphorylation modulates the expression of the target gene, cyclin B1. Since it is likely that Thr247 phosphorylation regulates DNA binding activity to multiple HOX11 target sequences, it is conceivable that phosphorylation functions to regulate the expression of HOX11 target genes involved in the control of the mitotic spindle checkpoint. more...

BackgroundWhile prostate cancer can often manifest as an indolent disease, the development of locally-advanced or metastatic disease can cause significant morbidity or mortality. Elucidation of molecular mechanisms contributing to disease progression is crucial for more accurate prognostication and effective treatments. R-Spondin 3 (RSPO3) is a protein previously implicated in the progression of colorectal and lung cancers. However, a role for RSPO3 in prostate cancer prognosis and behaviour has not been explored.MethodsWe compare the relative levels of RSPO3 expression between normal prostate tissue and prostate cancer in two independent patient cohorts (Taylor and GSE70768-Cambridge). We also examine the association of biochemical relapse with RSPO3 levels in these cohorts. For elucidation of the biological effect of RSPO3, we use siRNA technology to reduce the levels of RSPO3 in established prostate cancer cell lines, and perform in vitro proliferation, invasion, western blotting for EMT markers and clonogenic survival assays for radiation resistance. Furthermore, we show consequences of RSPO3 knockdown in an established chick chorioallantoic membrane (CAM) assay model of metastasis.ResultsRSPO3 levels are lower in prostate cancer than normal prostate, with a tendency for further loss in metastatic disease. Patients with lower RSPO3 expression have lower rates of biochemical relapse-free survival. SiRNA-mediated loss of RSPO3 results in no change to clonogenic survival and a lower proliferative rate, but increased invasiveness in vitro with induction of epithelial-mesenchymal transition (EMT) markers. Consistent with these results, lower RSPO3 expression translates to greater metastatic capacity in the CAM assay. Together, our preclinical findings identify a role of RSPO3 downregulation in prostate cancer invasiveness, and provide a potential explanation for how RSPO3 functions as a positive prognostic marker in prostate cancer. more...