Jumonji domain containing 2A (JMJD2A) is a potential cancer-associated gene that may be involved in human breast cancer. The present study aimed to investigate suppressive effects on the MCF-7 human breast cancer cell line by transfection with JMJD2A-specific siRNA. Quantitative real-time PCR and western blot analysis were used to detect the expression levels of JMJD2A. Flow cytometric (FCM) analysis and WST-8 assay were used to evaluate cell proliferation. Boyden chambers were used in cell migration and invasion assays to evaluate the cell exercise capacity. Expression levels of JMJD2A mRNA and protein in the siRNA group were both downregulated successfully by transfection. FCM results showed that the percentage of cells in the G0/G1 phase in the siRNA group was significantly greater than that in the blank (P<0.05) and negative control groups (P<0.05). Additionally, the mean absorbance in the siRNA group was significantly lower (P<0.05), as observed by WST-8 assay. Moreover, a decreased number of migrated cells in the siRNA group was observed (P<0.05) using a cell migration and invasion assay. These data indicated that knockdown of JMJD2A may cause inhibition of proliferation, migration and invasion of MCF-7 cells. This study provides a new perspective in understanding the molecular mechanisms underlying the progression of breast cancer and offers a potential therapeutic target for breast cancer.
jumonji domain containing 2A; transfection; invasion; proliferation; migration
Previous data demonstrate that JMJD2A is a cancer-associated gene and may be involved in human breast cancer by demethylation of H3K9me3. The aim of this study was to investigate depressive effects on JMJD2A by transfection with JMJD2A-sepcific siRNA in human breast cancer cell line MDA-MB-231 and effects on cell proliferation, invasion and migration. JMJD2A-specific siRNA was chemically synthesised and transfected into human breast cancer cell line MDA-MB-231. Expression levels of JMJD2A were detected by quantitative real-time PCR and Western blot analysis. Cells proliferation was evaluated by using flow cytometric anlysis and MTT assay. The abilities of invasion and migration were evaluated by cell migration and invasion assay with Boyden chambers. The results showed that the transfection was successful and expression levels of JMJD2A mRNA and protein in siRNA group were both down-regulated. By MTT assay, the mean actual absorbance in siRNA group was significantly lower than that in blank control group (P < 0.05) and negative control group (P < 0.05). In addition, the percentage of cells in G0/G1 phase in siRNA group was significantly more than that in blank control group (P < 0.05) and negative control group (P < 0.05). Furthermore, by cell invasion and migration assay, the decreased number of migrated cells in siRNA group was observed (P < 0.05). These data imply that silencing JMJD2A gene could result in cell cycle change and proliferation inhibition, and lead to suppress tumor cell invasion and migration. It provides a new perspective in understanding the pleiotropic functions of JMJD2A and its contribution to human breast cancer.
JMJD2A; transfection; proliferation; invasion; migration
P2X receptors participate in cardiovascular regulation and disease. After myocardial ischemic injury, sensory–sympathetic coupling between rat cervical DRG nerves and superior cervical ganglia (SCG) facilitated sympathoexcitatory action via P2X7 receptor. The results showed that after myocardial ischemic injury, the systolic blood pressure, heart rate, serum cardiac enzymes, IL-6, and TNF-α were increased, while the levels of P2X7 mRNA and protein in SCG were also upregulated. However, these alterations diminished after treatment of myocardial ischemic (MI) rats with the P2X7 antagonist oxATP. After siRNA P2X7 in MI rats, the systolic blood pressure, heart rate, serum cardiac enzymes, the expression levels of the satellite glial cell (SGC) or P2X7 were significantly lower than those in MI group. The phosphorylation of ERK 1/2 in SCG participated in the molecular mechanism of the sympathoexcitatory action induced by the myocardial ischemic injury. Retrograde tracing test revealed the sprouting of CGRP or SP sensory nerves (the markers of sensory afferent fibers) from DRG to SCG neurons. The upregulated P2X7 receptor promoted the activation of SGCs in SCG, resulting in the formation of sensory–sympathetic coupling which facilitated the sympathoexcitatory action. P2X7 antagonist oxATP could inhibit the activation of SGCs and interrupt the formation of sensory–sympathetic coupling in SCG after the myocardial ischemic injury. Our findings may benefit the treatment of coronary heart disease and other cardiovascular diseases.
P2X7 receptor; Superior cervical ganglia; Dorsal root ganglia; Myocardial ischemic injury; Sensory–sympathetic coupling
The decline of photosynthesis in plants under low sink demand is well known. Previous studies focused on the relationship between stomatal conductance (gs) and net photosynthetic rate (Pn). These studies investigated the effect of changes in Photosystem II (PSII) function on the Pn decline under low sink demand. However, little is known about its effects on different limiting steps of electron transport chain in PSII under this condition.
Two-month-old bean plants were processed by removing pods and flowers (low sink demand). On the 1st day after low sink demand treatment, a decline of Pn was accompanied by a decrease in gs and internal-to-ambient CO2 concentration ratio (Ci/Ca). From the 3rd to 9th day, Pn and gs declined continuously while Ci/Ca ratio remained stable in the treatment. Moreover, these values were lower than that of control. Wk (a parameter reflecting the damage to oxygen evolving complex of the donor side of PSII) values in the treatment were significantly higher than their corresponding control values. However, RCQA (a parameter reflecting the number of active RCs per excited cross-section of PSII) values in the treatment were significantly lower than control from the 5th day. From the 11th to 21st day, Pn and gs of the treatment continued to decline and were lower than control. This was accompanied by a decrease of RCQA, and an increase of Wk. Furthermore, the quantum yield parameters φPo, φEo and ψEo in the treatment were lower than in control; however, Ci/Ca values in the treatment gradually increased and were significantly higher than control on the 21st day.
Stomatal limitation during the early stage, whereas a combination of stomatal and non-stomatal limitation during the middle stage might be responsible for the reduction of Pn under low sink demand. Non-stomatal limitation during the late stages after the removal of the sink of roots and pods may also cause Pn reduction. The non-stomatal limitation was associated with the inhibition of PSII electron transport chain. Our data suggests that the donor side of PSII was the most sensitive to low sink demand followed by the reaction center of PSII. The acceptor side of PSII may be the least sensitive.
The aim of the present study was to perform a retrospective analysis to investigate the outcome and toxicity of radiation (RT) and chemoradiation (CRT) in elderly, inoperable patients >70 years old. Between 2003 and 2012, 1,024 patients with squamous cell carcinoma (SCC) of the esophagus were treated at the Department of Thoracic Cancer, West China Hospital (Chengdu, China). Of these patients, 37 were >70 years old and had not undergone surgery, and were selected for analysis. Of these 37 patients, CRT had been administered to 20 (54%). Actuarial survival rates were determined by the Kaplan-Meier method. The one-year survival rate in the CRT group (n=20) was 85%, while 35% of patients in the RT group (n=17) survived for more than one year. The overall and progression-free survival in the CRT group versus the RT group were 17 months [95% confidence interval (CI), 11.861–22.139] versus eight months (95% CI, 6.674–9.326) (P=0.013) and 14 months (95% CI, 9.617–18.383) versus five months (95% CI, 2.311–7.689) (P=0.01), respectively. Patients irradiated with a dose of >50 Gy exhibited an improved survival rate compared with patients who received a dose of ≤50 Gy (18 vs. 14 months; P=0.049). Furthermore, patients with an Eastern Cooperative Oncology Group (ECOG) score of ≤1 had an improved prognosis compared with those with an ECOG score of 2 (14 vs. seven months; P=0.006). The two regimens were well-tolerated and there were no therapy-associated mortalities. The current retrospective study indicated that patients of >70 years old with inoperable esophageal SCC and a good ECOG score exhibit comparably better safety levels with CRT and improved survival rates compared with RT alone.
esophageal squamous cancer; elderly; chemoradiation; radiation; toxicity
Retinal synaptic connections and function are developmentally regulated. Retinal synaptic activity plays critical roles in the development of retinal synaptic circuitry. Dopamine receptors have been thought to play important roles in the activity-dependent synaptic plasticity in central nervous system. The primary goal of this study is to determine whether dopamine D1 receptor regulates the activity-dependent development of retinal light responsiveness. Accordingly, we recorded electroretinogram from wild type mice and mice with genetic deletion of D1 dopamine receptor (D1−/− mice) raised under cyclic light conditions and constant darkness. Our results demonstrated that D1−/− mice have reduced amplitudes of all three major components of electroretinogram in adulthood. When the relative strength of the responses is considered, the D1−/− mice have selective reduction of the amplitudes of a-wave and oscillatory potentials evoked by low-intermediate intensities of lights. During postnatal development, D1−/− mice have increased amplitude of b-wave at the time of eye-opening but reduced developmental increase of the amplitude of b-wave after eye opening. Light deprivation from birth significantly reduced the amplitudes of b-wave and oscillatory potentials, increased the outer retinal light response gain and altered the light response kinetics of both a- and b-waves of wild type mice. In D1−/− mice, the effect of dark rearing on the amplitude of oscillatory potentials was diminished and dark rearing induced effects on the response gain of outer retina and the kinetics of a-wave were reversed. These results demonstrated roles of dopamine D1 receptor in the activity-dependent functional development of mouse retina.
A critical observation in sporadic cancers is that not all individuals are equally prone to developing cancer following exposure to a given environmental carcinogen. Epidemiological studies have suggested that the difference in the timing of cancer onset in response to exogenous DNA damage is likely attributable to genetic variations, such as those associated with base excision repair genes. To test this long-standing hypothesis and elucidate how a genetic variation in the base excision repair gene flap endonuclease 1 (FEN1) results in susceptibility to environment insults and causes cancer, we established a mutant mouse model carrying a point mutation (E160D) in Fen1. We demonstrate that the E160D mutation impairs the ability of FEN1 to process DNA intermediate structures in long-patch base excision repair using nuclear extracts or reconstituted purified base excision repair proteins. E160D cells were more sensitive to the base damaging agents methylnitrosourea and hydrogen peroxide, leading to DNA strand breaks, chromosomal breakage, and chromosome instabilities in response these DNA insults. We further show that E160D mice are significantly more susceptible to exposure to methylnitrosourea and develop lung adenocarcinoma. Thus, our current study demonstrates that a subtle genetic variation (E160D) in base excision repair genes (FEN1) may cause a functional deficiency in repairing base damage, such that individuals carrying the mutation or similar mutations are predisposed to chemical-induced cancer development.
FEN1; Long-patch base excision repair; methylnitrosourea; tetraploidy; aneuploidy; cancer
Glomerular podocytes are highly differentiated cells whose foot processes, which are mainly maintained by the architecture of actin filaments, have a unique morphology. A rearrangement of F-actin in podocytes causes changes in their motility that involve foot process effacement and proteinuria in glomerular diseases. Members of the Rho family small GTPases, especially RhoA, Rac1, and Cdc42, are key molecules in the regulation of actin cytoskeleton rearrangement. Our previous study showed that angiopoietin-like 3 (Angptl3) can increase the motility of podocytes in vitro. In this study, we found that recombinant Angptl3 treatment, together with the activation of Rac1, could cause F-actin rearrangement in podocytes. We also found that these effects could be blocked by an integrin αVβ3 inhibitor, implicating integrin αVβ3 as the Angptl3 receptor in its effects on actin cytoskeleton rearrangement. In addition, we studied the molecular pathway for this process. Our results showed that in podocytes, Angptl3 could induce actin filament rearrangement, mainly in lamellipodia formation, and that this process was mediated by integrin αVβ3-mediated FAK and PI3K phosphorylation and Rac1 activation. Our results might provide a new explanation for the effect of Angptl3 on increasing podocyte motility.
Breast capillary hemangioma is a type of benign vascular tumor which is rarely seen. Little is known about its presentation on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Here, we describe a case of suspicious breast lesion detected by DCE-MRI and pathologically confirmed as capillary hemangioma. Our case indicates that a small mass with a superficial location, clear boundary, and homogeneous enhancement on DCE-MRI indicates the possible diagnosis of hemangioma, whereby even the lesion presents a washout type curve.
Mammography; Ultrasound; Dynamic contrast-enhanced magnetic resonance imaging; Hemangioma
TAL (transcriptional activator-like) effectors (TALEs) are DNA-binding proteins, containing a modular central domain that recognizes specific DNA sequences. Recently, the crystallographic studies of TALEs revealed the structure of DNA-recognition domain. In this article, molecular dynamics (MD) simulations are employed to study two crystal structures of an 11.5-repeat TALE, in the presence and absence of DNA, respectively. The simulated results indicate that the specific binding of RVDs (repeat-variable diresidues) with DNA leads to the markedly reduced fluctuations of tandem repeats, especially at the two ends. In the DNA-bound TALE system, the base-specific interaction is formed mainly by the residue at position 13 within a TAL repeat. Tandem repeats with weak RVDs are unfavorable for the TALE-DNA binding. These observations are consistent with experimental studies. By using principal component analysis (PCA), the dominant motions are open-close movements between the two ends of the superhelical structure in both DNA-free and DNA-bound TALE systems. The open-close movements are found to be critical for the recognition and binding of TALE-DNA based on the analysis of free energy landscape (FEL). The conformational analysis of DNA indicates that the 5′ end of DNA target sequence has more remarkable structural deformability than the other sites. Meanwhile, the conformational change of DNA is likely associated with the specific interaction of TALE-DNA. We further suggest that the arrangement of N-terminal repeats with strong RVDs may help in the design of efficient TALEs. This study provides some new insights into the understanding of the TALE-DNA recognition mechanism.
Miniature inverted-repeat transposable elements (MITEs) are a specific group of nonautonomous DNA transposons, and they are distributed in a wide range of hosts. However, the origin and evolutionary history of MITEs in eukaryotic genomes remain unclear. In this study, six MITEs were identified in the silkworm (Bombyx mori). Five elements are grouped into four known superfamilies of DNA transposons, and one represents a novel class of MITEs. Unexpectedly, six similar MITEs are also present in the triatomine bug (Rhodnius prolixus) that diverged from the common ancestor with the silkworm about 370 Ma. However, they show different lengths in two species, suggesting that they are different derivatives of progenitor transposons. Three direct progenitor transposons (Sola1, hobo/Ac/Tam [hAT], and Ginger2) are also identified in some other organisms, and several lines of evidence suggested that these autonomous elements might have been independently and horizontally transferred into their hosts. Furthermore, it is speculated that the twisted-wing parasites may be the candidate vectors for these horizontal transfers. The data presented in this study provide some new insights into the origin and evolutionary history of MITEs in the silkworm and triatomine bug.
MITEs; origin; evolution; Bombyx mori; Rhodnius prolixus
Sucrose isomerase NX-5 from Erwiniarhapontici efficiently catalyzes the isomerization of sucrose to isomaltulose (main product) and trehalulose (by-product). To investigate the molecular mechanism controlling sucrose isomer formation, we determined the crystal structures of native NX-5 and its mutant complexes E295Q/sucrose and D241A/glucose at 1.70 Å, 1.70 Å and 2.00 Å, respectively. The overall structure and active site architecture of NX-5 resemble those of other reported sucrose isomerases. Strikingly, the substrate binding mode of NX-5 is also similar to that of trehalulose synthase from Pseudomonasmesoacidophila MX-45 (MutB). Detailed structural analysis revealed the catalytic RXDRX motif and the adjacent 10-residue loop of NX-5 and isomaltulose synthase PalI from Klebsiella sp. LX3 adopt a distinct orientation from those of trehalulose synthases. Mutations of the loop region of NX-5 resulted in significant changes of the product ratio between isomaltulose and trehalulose. The molecular dynamics simulation data supported the product specificity of NX-5 towards isomaltulose and the role of the loop330-339 in NX-5 catalysis. This work should prove useful for the engineering of sucrose isomerase for industrial carbohydrate biotransformations.
In the title compound, C27H22N2O4, the two indole ring systems are approximately perpendicular to each other, with a dihedral angle of 84.5 (5)° between their planes; the benzene ring is twisted with respect to the two indole ring systems at angles of 78.5 (5) and 86.5 (3)°. In the crystal, molecules are linked by N—H⋯O hydrogen bonds, weak C—H⋯O and C—H⋯N hydrogen bonds, and C—H⋯π interactions into a three-dimensional supramolecular architecture.
Background. To investigate the specific link between lung and large intestine. Methods. Rat COPD-like model was prepared. Mirabilite or Chinese rhubarb was administrated intragastrically to stimulate the large intestine. Histological analysis of lung inflammation was assessed. The tissues levels of SP, VIP, NK1R, VIPR1, and VIPR2 were measured by using ELISA kits. In addition, mouse model of allergic asthma was prepared. Mirabilite was administrated intragastrically to stimulate the large intestine. Airway responsiveness and lung inflammation were assessed. The tissues levels of SP, VIP, NKA, NKB, NK1R, VIPR1, and VIPR2 were measured by using ELISA kits. Results. Stimulating the intestine with Mangxiao or Dahuang, SP, NK-1R, VIP, VIPR1, and VIPR2 were significantly increased in intestine tissues of rats with COPD and mice with asthma. Meanwhile, the SP and NK1R were significantly decreased, while VIP, VIPR1, and VIPR2 were significantly increased in lung tissues. An abnormal secretion of SP and VIP can be observed in other tissues; however, no marked changes were found in the receptors. The NKA and NKB levels were similar in lung tissues of mice with asthma among groups. Conclusions. Stimulating intestine with Mangxiao or Dahuang can specifically regulate the secretion of SP, VIP, and the receptors in lung tissues.
STAT is the backward position of cytokine and growth factor receptors in the nucleus, STAT dimers could bind to DNA and induce transcription of specific target genes. Several lines of evidence support the important roles of STAT, especially STAT5, in carcinogenesis. The overexpression of STAT 5 is related to the differentiation and apoptosis of tumor cells. However, the role of STAT5 in esophageal squamous cell carcinoma remains unclear.
The siRNA vectors aiming to STAT5 gene were constructed. STAT5 siRNA was transfected into Eca-109 cells by Lipofectamine™2000. Expression of STAT5、Bcl-2 and Cyclin D1 were analyzed by Western blot and RT-PCR. Eca-109 cells proliferation was determined by MTT. Eca-109 cell cycle and apoptosis were detected by the flow cytometry. Boyden chamber was used to evaluate the invasion and metastasis capabilities of Eca-109 cells.
The double strands oligonucleotide of siRNA aiming to STAT5 was successfully cloned into the pRNAT-U6.1 vector, and the target sequence coincided with the design. RT-PCR and Western blotting detection demonstrated that the expression levels of STAT5、Bcl-2 and Cyclin D1 gene were obviously decreased in Eca-109 cells transfected with STAT5 siRNA. STAT5 siRNA could suppress the proliferation of Eca-109 cells. The proportion of S and G2/M period frequency was significantly decreased (p < 0.05). The proportion of G0/G1 period frequency was significantly increased (p < 0.05). The average amount of cells penetrating Matrigel was significantly decreased (p < 0.05).
STAT5 silenced by siRNA could induce the apoptosis and suppress the proliferation、invasion and metastasis of esophageal carcinoma cell line Eca-109, which indicated STAT5 might be a novel therapeutic strategy for the human ESCC.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1351913072103000
STAT5; siRNA; Proliferation; Cell cycle; Apoptosis
The main purpose of this paper is to study the exceptional values of meromorphic function and its derivative on annulus. We also give some theorems and corollaries about exceptional values of meromorphic function on the annulus, which are the improvement of the previous results given by Chen and Wu.
We previously reported that Axin1 (Axin) is down-regulated in many cases of lung cancer, and X-ray irradiation increased Axin expression and inhibited lung cancer cells. The mechanisms, however, were not clear.
Four lung cancer cell lines were used to detect the methylation status of Axin with or without X-ray treatment. Real-time PCR was used to quantify the expression of Axin, and western blot analysis was applied to measure protein levels of Axin, β-catenin, Cyclin D1, MMP-7, DNMTS, MeCP2 and acetylated histones. Flow cytometric analysis, colony formation assay, transwell assay and xenograft growth experiment were used to study the biological behavior of the cells with hypermethylated or unmethylated Axin gene after X-ray treatment.
Hypermethylated Axin gene was detected in 2 of 4 cell lines, and it correlated inversely with Axin expression. X-ray treatment significantly up-regulated Axin expression in H446 and H157 cells, which possess intrinsic hypermethylation of the Axin gene (P<0.01), but did not show up-regulation in LTE and H460 cells, which have unmethylated Axin gene. 2Gy X-ray significantly reduced colony formation (from 71% to 10.5%) in H157 cells, while the reduction was lower in LTE cells (from 71% to 20%). After X-ray irradiation, xenograft growth was significantly decreased in H157 cells (from 1.15 g to 0.28 g) in comparison with LTE cells (from 1.06 g to 0.65 g). Significantly decreased cell invasiveness and increased apoptosis were also observed in H157 cells treated with X-ray irradiation (P<0.01). Down-regulation of DNMTs and MeCP2 and up-regulation of acetylated histones could be detected in lung cancer cells.
X-ray-induced inhibition of lung cancer cells may be mediated by enhanced expression of Axin via genomic DNA demethylation and histone acetylation. Lung cancer cells with a different methylation status of the Axin gene showed different radiosensitivity, suggesting that the methylation status of the Axin gene may be one important factor to predict radiosensitivity of the tumor.
Axin; Methylation; Proliferation; Invasiveness; Radiosensitivity
The silkworm, Bombyx mori, is one of the major insect model organisms, and its draft and fine genome sequences became available in 2004 and 2008, respectively. Transposable elements (TEs) constitute ∼40% of the silkworm genome. To better understand the roles of TEs in organization, structure and evolution of the silkworm genome, we used a combination of de novo, structure-based and homology-based approaches for identification of the silkworm TEs and identified 1308 silkworm TE families. These TE families and their classification information were organized into a comprehensive and easy-to-use web-based database, BmTEdb. Users are entitled to browse, search and download the sequences in the database. Sequence analyses such as BLAST, HMMER and EMBOSS GetORF were also provided in BmTEdb. This database will facilitate studies for the silkworm genomics, the TE functions in the silkworm and the comparative analysis of the insect TEs.
Database URL: http://gene.cqu.edu.cn/BmTEdb/.
Inflammatory mediators, many of which activate the signaling of nuclear factor kappa B (NFκB), have received increasing attention in the field of neurogenesis. NFκB signaling regulates neurite outgrowth and neural plasticity as well as the proliferation/apoptosis and terminal differentiation of neural stem cells (NSCs). Early neurogenesis from NSCs produces identical progeny through symmetric division and committed daughter cells through asymmetric division. Here, we show that NFκB signaling is required for NSC initial differentiation. The canonical IKKβ/IκBα/ p65 pathway is activated during the initial stages of neural differentiation induced by treatment with TNFα or with- drawal of epidermal growth factor/basic fibroblast growth factor. NSC-specific inhibition of NFκB in transgenic mice causes an accumulation of Nestin+/Sox2+/glial fibrillary acidic protein+ NSCs. Inhibition of NFκB signaling in vitro blocks differentiation and asymmetric division and maintains NSCs in an undifferentiated state. The induction of initial differentiation and asymmetry by NFκB signaling occurs through the inhibition of C/EBPβ expression. Our data reveal a novel function of NFκB signaling in early neurogenesis and provide insight into the molecular mechanisms underlying neurodevelopmental disorders and neurodegenerative diseases.
Neural stem cells; Nuclear factor kappa B; Neurogenesis; C/EBPβ; Glial fibrillary acidic protein; Cell division
♦ Background, Objectives, and Methods: The number of patients on chronic peritoneal dialysis (CPD) is increasing rapidly on a global scale. We analyzed the International Pediatric Peritoneal Dialysis Network (IPPN) registry, a global database active in 33 countries spanning a wide range in gross national income (GNI), to identify the impact of economic conditions on CPD practices and outcomes in children and adolescents.
♦ Results: We observed close associations of GNI with the fraction of very young patients on dialysis, the presence and number of comorbidities, the prevalence of patients with unexplained causes of end-stage kidney disease, and the rate of culture-negative peritonitis. The prevalence of automated PD increased with GNI, but was 46% even in the lowest GNI stratum. The GNI stratum also affected the use of biocompatible peritoneal dialysis fluids, enteral tube feeding, calcium-free phosphate binders, active vitamin D analogs, and erythropoiesis-stimulating agents (ESAs). Patient mortality was strongly affected by GNI (hazard ratio per $10 000: 3.3; 95% confidence interval: 2.0 to 5.5) independently of young patient age and the number of comorbidities present. Patients from low-income countries tended to die more often from infections unrelated to CPD (5 of 9 vs 15 of 61, p = 0.1). The GNI was also a strong independent predictor of standardized height (p < 0.0001), adding to the impact of congenital renal disease, anuria, age at PD start, and dialysis vintage. Patients from the lower economic strata (GNI < $18 000) had higher serum parathyroid hormone (PTH) and lower serum calcium, and achieved lower hemoglobin concentrations. No impact of GNI was observed with regard to CPD technique survival or peritonitis incidence.
♦ Conclusions: We conclude that CPD is practiced successfully, albeit with major regional variation related to economic differences, in children around the globe. The variations encompass the acceptance of very young patients and those with associated comorbidities to chronic dialysis programs, the use of automated PD and expensive drugs, and the diagnostic management of peritonitis. These variations in practice related to economic difference do not appear to affect PD technique survival; however, economic conditions seem to affect mortality on dialysis and standardized height, a marker of global child morbidity.
Children; economics; developing countries; patient survival; technique survival; growth; registry
Noninvasive imaging techniques have been considered important strategies in the clinic to monitor tumor early response to therapy. In the present study, we applied RGD peptides conjugated to iron oxide nanoparticles (IONP-RGD) as contrast agents in magnetic resonance imaging (MRI) to noninvasively monitor the response of a vascular disrupting agent VEGF121/rGel in an orthotopic glioblastoma model. RGD peptides were firstly coupled to IONPs coated with a crosslinked PEGylated amphiphilic triblock copolymer. In vitro binding assays confirmed that cellular uptake of particles was mainly dependent on the interaction between RGD and integrin αvβ3 of human umbilical vein endothelial cells (HUVEC). The tumor targeting of IONP-RGD was observed in an orthotopic U87 glioblastoma model. Finally, noninvasive monitoring of the tumor response to VEGF121/rGel therapy at early stages of treatment was successfully accomplished using IONP-RGD as a contrast agent for MRI, a superior method over common anatomical approaches which are based on tumor size measurements. This preclinical study can accelerate anticancer drug development and promote clinical translation of nanoprobes.
Magnetic resonance imaging (MRI); Iron oxide nanoparticles (IONPs); RGD peptides; Tumor targeting; Therapy response
To identify risk factors for HIV infection among men who have sex with men (MSM) and to provide a theoretical basis for prevention interventions. Between December 2011 and August 2012, a case–control study was conducted among MSM who underwent voluntary counselling and testing for HIV. Confirmed HIV-positive MSM were included in the case group, and HIV-negative MSM were included in the control group. Information on possible risk factors was collected by a survey questionnaire and a qualitative interview. The results of a conditional logistic regression showed that the following were influencing factors for HIV infection: average monthly income between 2001 and 3000 Yuan (odds ratio (OR)=6.341, 95% CI: 1.714–12.544), only sometimes using condoms when having anal sex with men in the last 6 months (OR=7.601, 95% CI: 1.359–23.083), having HIV-positive sex partners (OR=5.273, 95% CI: 1.572–17.691), rectal trauma with bleeding in the last 6 months (OR=2.947, 95% CI: 1.308–6.638), not using condoms at last sexual encounter (OR=1.278, 95% CI: 1.012–5.595), engaging in commercial sex (OR=5.925, 95% CI: 1.923–13.890) and having more than 16 sex partners in the last 6 months (OR=1.175, 95% CI: 1.021–1.353). These seven factors were the risk factors of HIV infection (OR>1). However, having anal sex less than 10 times in the previous 1 month (OR=0.002, 95% CI: 0.000–0.287) was a protective factor against HIV infection among MSM (OR<1), and insertive (OR=0.116, 95% CI: 0.000–0.236) (OR<1) anal intercourse influenced HIV infection. Interventions should be targeted at MSM whose average monthly income is between 2001 and 3000 Yuan, and who engage in commercial sex. In addition, the importance of using condoms at every sexual encounter should be emphasised in health education, as should the treatment of rectal trauma with bleeding. Finally, MSM should decrease the number of sex partners and frequency of anal sex to decrease the rate of HIV infection.
case–control study; HIV infection; influencing factors; men who have sex with men (MSM)
Adenocarcinoma of the rete testis is very rare. There is still little knowledge about its etiology and pathogenesis. Herein, we present a case of rete testis adenocarcinoma in a 36-year-old Chinese male. The tumor was predominantly composed of irregular small tubules and papillary structures with cuboidal or polygonal cells. In peripheral area of the tumor, the remaining normal rete testis and adenomatous hyperplasia of the rete testis could also be seen, indicating the possible relationship between adenomatous hyperplasia and adenocarcinoma. In addition, the patient underwent a left hydrocelectomy because of the existence of hydrocele 3 years ago. But, it is unclear whether hydrocele and hydrocelectomy is its cause or just the early clinical presentation of the adenocarcinoma.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6757609119625499
Adenocarcinoma; Rete testis; Adenomatous hyperplasia
CXC chemokine receptor 4 was found to be expressed by many different types of human cancers and its expression has been correlated with tumor aggressiveness, poor prognosis and resistance to chemotherapy. However the effect of CXCR4 on the esophageal carcinoma cells remains unclear, the present study explored the effects of CXCR4 siRNA on proliferation and invasion of esophageal carcinoma KYSE-150 and TE-13 cells. Two siRNA sequence targeting CXCR4 gene were constructed and then were transfected into KYSE-150 and TE-13 cells by Lipofectamine™2000. Changes of CXCR4 mRNA and protein were analyzed by qRT-PCR and Western blot. Effect of CXCR4 siRNA on KYSE-150 and TE-13 cells proliferation was determined by MTT. Transwell invasion assay was used to evaluate the invasion and metastasis of KYSE-150 and TE-13 cells. Tumor growth was assessed by subcutaneous inoculation of cells into BALB/c nude mice. qRT-PCR and Western blot demonstrate that the expression level of CXCR4 gene were obviously decreased in KYSE-150 and TE-13 cells transfected with CXCR4 targeting siRNA expression vectors. The average amount of cells transfected with CXCR4 siRNA penetrating Matrigel was significantly decreased (p<0.05). Injection of CXCR4 siRNA transfected cells inhibited tumor growth in a xenograft model compared with blank and negative control groups (p <0.05). CXCR4 silenced by siRNA could suppress the proliferation, invasion and metastasis of esophageal carcinoma cell lines KYSE-150 and TE-13 in vitro and in vivo. The results provide a theoretical and experimental basis for the gene therapy of ESCC using RNAi technology based on CXCR4 target site.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3502376691001138
Esophageal carcinoma; CXCR4; Proliferation; Invasion
Epithelioid hemangioendothelioma is a relatively uncommon lesion usually presenting in soft tissues. The occurrence in the mediastinum is exceptional rare. Histologically, this tumor is characterized by epithelioid cells with intracytoplasmic vacuoles in a hyalinized or mucinous stroma. Occasionally, spindle cells or osteoclast-like giant cells can be observed. Herein, we present a case of epithelioid hemangioendothelioma in a 38 year-old Chinese male. The tumor was predominantly composed of abundant spindle cells with marked atypia and scattered osteoclast-like giant cells reminiscent of malignant fibrous histiocytoma. The unusual histological appearance can pose a great diagnostic challenge. It may be easily misdiagnosed, especially if the specimen is limited or from fine-needle aspiration.
Epithelioid hemangioendothelioma; Mediastinum; Osteoclast-like giant cells; Malignant fibrous histiocytoma