[Cystic echinococcosis of the waist and hip: a case report].

A patient with cystic echinococcosis was presented with primary lesions in the waist and hip. The case was misdiagnosed as subcutaneous abscess at initial diagnosis, and then definitively diagnosed as echinococcosis by means of imaging examinations and anti-Echinococcus antibody test. This case was reported with aims to improve the awareness of cystic echinococcosis among clinical physicians to avoid and reduce the misdiagnosis and missing diagnosis.

Metabolic syndrome-related SNPs in HLA and TNF7L2 may be risk factors for generalized pustular psoriasis in Chinese Han population.

Background: Generalized pustular psoriasis (GPP) is a rare and severe type of psoriasis. Previous studies have reported that metabolic syndrome and its components have been associated with psoriasis. Objective: To investigate the association of metabolic syndrome-related single-nucleotide polymorphisms (SNPs) and GPP in Chinese Han population. Materials and Methods: One hundred and thirty-six (136) GPP patients and 965 healthy controls were recruited in the study. Approximately, 4 ml peripheral venous blood was collected from each participant. After collection, second-generation sequencing was used to detect genetic polymorphism of 15 SNPs. The plink 1.07 software package was used for statistical analysis. Results: Rs805303 (p = 0.01, OR = 0.70) and rs3177928 (p = 3.18E-07, OR = 2.66) in HLA were significantly different between the two groups. Moreover, rs4506565 (p = 1.41E-03, OR = 2.72) and rs7901695 (p = 9.39E-04, OR = 2.82) in TCF7L2 were significantly associated with GPP in patients without a previous history of PsV. Genotype analysis of rs4506565 and rs7901695 showed that under the recessive model, genotype frequencies of rs4506565 (p = 0.00, OR = 18.52) and rs7901695 (p = 0.00, OR = 18.44) were significantly different between GPP patients and healthy controls. Conclusion: Rs805303 and rs3177928 in HLA may increase the risk of GPP in the Chinese Han population. TCF7L2 may be a risk factor for GPP in patients without a previous history of PsV.

Correction: The Rho/ROCK pathway for lysophosphatidic acid-induced proteolytic enzyme expression and ovarian cancer cell invasion.

The original version of this article contained an error in the published figures Fig 2 and Fig 3f, where the information was inadvertently duplicated. This error does not alter the conclusions of the paper. The corrected figures are published in this correction notice. The authors sincerely apologize for this error.

Functional characterization of O-methyltransferases used to catalyse site-specific methylation in the post-tailoring steps of pradimicin biosynthesis.

AIMS: To identify the roles of the two O-methyltransferase homologous genes pdmF and pdmT in the pradimicin biosynthetic gene cluster of Actinomadura hibisca P157-2. METHODS AND RESULTS: Pradimicins are pentangular polyphenol antibiotics synthesized by bacterial type II polyketide synthases (PKSs) and tailoring enzymes. Pradimicins are naturally derivatized by combinatorial O-methylation at two positions (i.e., 7-OH and 11-OH) of the benzo[α]naphthacenequinone structure. PdmF and PdmT null mutants (PFKO and PTKO) were generated. PFKO produced the 11-O-demethyl shunt metabolites 11-O-demethylpradimicinone II (1), 11-O-demethyl-7-methoxypradimicinone II (2), 11-O-demethylpradimicinone I (3) and 11-O-demethylpradimicin A (4), while PTKO generated the 7-O-demethyl derivatives pradimicinone II (5) and 7-hydroxypradimicin A (6). Pradimicinones 1, 2, 3, and 5 were fed to a heterologous host Escherichia coli harbouring expression plasmid pET-22b::pdmF or pET-28a::pdmT. PdmF catalysed 11-O-methylation of pradimicinones 1, 2, and 3 regardless of O-methylation at the C-7 position, while PdmT was unable to catalyse 7-O-methylation when the C-11 hydroxyl group was methylated (5). CONCLUSIONS: PdmF and PdmT were involved in 11-O- and 7-O-methylations of the benzo[α]naphthacenequinone moiety of pradimicin, respectively. Methylation of the C-7 hydroxyl group precedes methylation of the C-11 hydroxyl group in pradimicin biosynthesis. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first reported demonstration of the functions of PdmF and PdmT for regiospecific O-methylation, which contributes to better understanding of the post-PKS modifications in pradimicin biosynthesis as well as to rational engineering of the pradimicin biosynthetic machinery.

Comparison of reversal with neostigmine of low-dose rocuronium vs. reversal with sugammadex of high-dose rocuronium for a short procedure.

Some short procedures require deep neuromuscular blockade, which needs to be reversed at the end of the procedure. Forty-four patients undergoing elective laryngeal micro-surgery were randomly allocated into two groups: rocuronium 0.45 mg.kg-1 with neostigmine (50 µg.kg-1 with glycopyrrolate 10 µg.kg-1 ) reversal (moderate block group) vs. rocuronium 0.90 mg.kg-1 with sugammadex (4 mg.kg-1 ) reversal (deep block group). The primary outcome was the intubating conditions during laryngoscopy secondary outcomes included recovery of neuromuscular block; conditions for tracheal intubation; satisfaction score as determined by the surgeon; onset of neuromuscular block; and postoperative sore throat. The onset of neuromuscular block was more rapid, and intubation conditions and ease of intra-operative laryngoscopy were more favourable, and the satisfaction score was lower in the moderate block group compared with the deep block group. No difference was found in the incidence of postoperative sore throat. In laryngeal micro-surgery, the use of rocuronium 0.9 mg.kg-1 with sugammadex for reversal was associated with better surgical conditions and a shorter recovery time than rocuronium 0.45 mg.kg-1 with neostigmine.

Two familial cases of Olmsted-like syndrome with a G573V mutation of the TRPV3 gene.

Olmsted syndrome (OS) is a rare disease, characterized by symmetrical, sharply defined, hyperkeratotic, mutilating plaques on the palms and soles, which are associated with periorificial keratotic plaques. Other clinical manifestations of OS include diffuse alopecia, leucokeratosis of the oral mucosa, onychodystrophy, hyperkeratotic linear streaks, follicular hyperkeratosis and constriction of the digits. A recent study identified de novo mutations in the gene for transient receptor potential vanilloid 3 (TRPV3), causing constitutive activation of the TRPV3 channel, as a cause of OS. We report familial inheritance of OS in a family from Mongolia, which was caused by a previously undescribed G573V point mutation in TRPV3. To date, mutations in the G573 residue of TRPV3 have been reported in seven cases of OS: G573S in five cases, and G573C and G573A mutations in one case each. We present a Mongolian familial case of G573V point mutation in TRPV3.

Single nucleotide polymorphisms of TNFAIP3 are associated with systemic lupus erythematosus in Han Chinese population.

The polymorphisms of tumour necrosis factor alpha-induced protein 3 (TNFAIP3) have been found to associate with several autoimmune diseases. This study aimed to explore the association of single nucleotide polymorphisms (SNPs) of TNFAIP3 gene with systemic lupus erythematosus (SLE) in Han Chinese. Thirty-two SNPs were genotyped in 284 patients with SLE and 630 controls using the ligation detection reaction (LDR) method. The quality control steps and statistical analyses were performed using the PLINK 1.07 package and HAPLOVIEW software. We found that 13 SNPs in TNFAIP3 showed significant association with SLE (P < 1.85 × 10(-3)), and all of them were in high linkage disequilibrium (LD). After conditioning on the SNP rs2230926, other 12 SNPs did not show association (P > 0.27). All 13 SNPs showed most significant association in the dominant model. In haplotype analysis, a long risk SNP haplotype (GCCCGTGTCATGG) showed most significant association (P = 1.00 × 10(-4)). In conclusion, our data suggest that TNFAIP3 is a susceptible gene for SLE in the Han Chinese population.

Self-expandable metal stents for malignant esophageal obstruction: a comparative study between extrinsic and intrinsic compression.

Self-expandable metal stents (SEMSs) are effective for malignant esophageal obstruction, but usefulness of SEMSs in extrinsic lesions is yet to be elucidated. This study is aimed at evaluating the clinical usefulness of SEMSs in the extrinsic compression compared with intrinsic. A retrospective review was conducted for 105 patients (intrinsic, 85; extrinsic, 20) with malignant esophageal obstruction who underwent endoscopic SEMSs placement. Technical and clinical success rates were evaluated and clinical outcomes were compared between extrinsic and intrinsic group. Extrinsic group was mostly pulmonary origin. Overall technical and clinical success rate was 100% and 91%, respectively, without immediate complications. Extrinsic and intrinsic group did not differ significantly in clinical success rate. The median stent patency time was 131.3 ± 85.8 days in intrinsic group while that of extrinsic was 54.6 ± 45.1 due to shorter survival after stent insertion. The 4-, 8-, and 12-week patency rates were 90.5%, 78.8%, and 64.9% respectively in intrinsic group, while stents of extrinsic group remained patent until death. Uncovered, fully covered, and double-layered stent were used evenly and the types did not influence patency in both groups. In conclusion, esophageal SEMSs can safely and effectively be used for malignant extrinsic compression as well as intrinsic.

Transcriptional repression of cancer stem cell marker CD133 by tumor suppressor p53.

Novel therapeutic strategies are needed to overcome cancer recurrence, metastasis, and resistance to chemo- and radiotherapy. Cancer stem cells (CSCs) are major contributors to the malignant transformation of cells due to their capacity for self-renewal. Although various CSC markers have been identified in several types of tumors, they are primarily used as cancer-prediction markers and for the isolation of CSC populations. CD133, one of the best-characterized CSC markers in distinct solid tumor types, was shown to be correlated with CSC tumor-initiating capacity; however, the regulation of CD133 expression and its function in cancer are poorly understood. Here, we show that CD133 expression is negatively regulated by direct binding of the p53 tumor suppressor protein to a noncanonical p53-binding sequence in the CD133 promoter. Binding of p53 recruits Histone Deacetylase 1 (HDAC1) to the CD133 promoter and subsequently suppresses CD133 expression by reducing histone H3 acetylation. Furthermore, CD133 depletion suppresses tumor cell proliferation, colony formation, and the expression of core stemness transcription factors including NANOG, octamer-binding transcription factor 4 (OCT4), SOX2, and c-MYC. Critically, the anti-proliferative effects of p53 are antagonized by rescue of CD133 expression in a p53 overexpressing cell line, indicating that the tumor suppressive activity of p53 might be mediated by CD133 suppression. Taken together, our results suggest that p53-mediated transcriptional regulation of CD133 is a key underlying mechanism for controlling the growth and tumor-initiating capacity of CSCs and provide a novel perspective on targeting CSCs for cancer therapy.

Automatic segmentation of juxta-pleural tumors from CT images based on morphological feature analysis.

Extraction of lung tumors is a fundamental step for further quantitative analysis of the tumor, but is challenging for juxta-pleural tumors due to the adhesion to the pleurae. An automatic algorithm for segmentation of juxta-pleural tumors based on the analysis of the geometric and morphological features was proposed. Initially, the lung is extracted by means of thresholding using 2D Otsu's method. Next a center point is suggested to find a starting point and endpoint of outward facing pleura. A model based on the variation of incline angle was adopted to identify potentially affected regions, and to full segment juxta-pleural tumors. The results were compared with the manual segmentation by two radiologists. Averaged for ten experimental datasets, the accuracy calculated by Dice index between the results of the algorithm and by the two radiologists is 91.2%. It indicates the proposed method has comparable accuracy with the experts (the inter-observer variability is 92.4%), but requests much less manual interactions. The proposed algorithm can be used for segmenting juxta-pleural tumors from CT images, and help improve the diagnosis, pre-operative planning and therapy response evaluation.

Menin mediates epigenetic regulation via histone H3 lysine 9 methylation.

Menin, encoded by the multiple endocrine neoplasia type 1 (MEN1) gene, is a tumor suppressor that leads to multiple endocrine tumors upon loss of its function. Menin functions as a transcriptional activator by tethering MLL complex to mediate histone H3 K4 methylation. It also functions as a repressor. However, the molecular mechanism of how menin contributes to the opposite outcome in gene expression is largely unknown. Here, we investigated the role of menin in the epigenetic regulation of transcription mediated by histone covalent modification. We show that the global methylation level of histone H3 K9, as well as H3 K4, was decreased in Men1(-/-) MEF cells. Consistently, menin was able to interact with the suppressor of variegation 3-9 homolog family protein, SUV39H1, to mediate H3 K9 methylation. This interaction decreased when patient-derived MEN1 mutation was introduced into the SUV39H1-interaction domain. We show that menin mediated different chromatin changes depending on target genes. Chromatin immunoprecipitation studies showed that menin directly associated with the GBX2 promoter and menin-dependent recruitment of SUV39H1 was essential for chromatin remodeling and transcriptional regulation. These results provide a molecular basis of how menin functions as a transcriptional repressor and suggest that menin-dependent integration of H3 K9 methylation might play an important role in preventing tumors.

The Rho/ROCK pathway for lysophosphatidic acid-induced proteolytic enzyme expression and ovarian cancer cell invasion.

Lysophosphatidic acid (LPA) is a biolipid that has diverse biological activities implicated in ovarian cancer initiation and progression. Previous studies have shown the critical role of the Rho/Rho-associated kinase (ROCK) pathway in LPA-induced ovarian cancer progression. However, detailed underlying mechanism by which the Rho/ROCK pathway induces ovarian cancer cell invasion is still incompletely understood. In the present study, we observed that the Rho/ROCK pathway is implicated in the production of proteolytic enzymes, leading to LPA-induced ovarian cancer cell invasion. LPA induced matrix metalloproteinase (MMP)-9 expression in CAOV-3 and PA-1 cells and urokinase-type plasminogen activator (uPA) expression in SKOV-3 cells. LPA-induced proteolytic enzyme expression was required for the invasion of ovarian cancer cells expressing corresponding enzymes. Pretreatment of cells with a pharmacological inhibitor of Rho/ROCK (Y-27632) or overexpression of a dominant-negative mutant of Rho (Rho N19) profoundly inhibited LPA-induced proteolytic enzyme expression as well as the invasive potential of ovarian cancer cells. In addition, transfection with dominant-negative Ras (Ras N17) significantly inhibited LPA-induced Rho activation as well as MMP-9 and uPA expression. Consistently, Y-27632 reduced LPA-induced nuclear factor (NF)-κB activation that is critical for proteolytic enzyme expression and cellular invasion. Collectively, we demonstrate a mechanism by which LPA promotes ovarian cancer progression through coordinate activation of a Ras/Rho/ROCK/NF-κB signaling pathway and the proteolytic enzyme secretion, providing novel biomarkers and promising therapeutic targets for ovarian cancer cell progression.

Lysophosphatidic acid augments human hepatocellular carcinoma cell invasion through LPA1 receptor and MMP-9 expression.

Lysophosphatidic acid (LPA), produced extracellularly by autotaxin (ATX), has diverse biological activities implicated in tumor initiation and progression, including increasing cell survival, angiogenesis, invasion and metastasis. ATX, LPA and the matrix metalloproteinase (MMP)-9 have all been implicated in hepatocellular carcinoma (HCC) invasion and metastasis. We, thus sought to determine whether ATX with subsequent LPA production and action, including induction of MMP-9 could provide a unifying mechanism. ATX transcripts and LPA receptor type 1 (LPA1) protein are elevated in HCC compared with normal tissues. Silencing or pharmacological inhibition of LPA1 significantly attenuated LPA-induced MMP-9 expression and HCC cell invasion. Further, reducing MMP-9 activity or expression significantly inhibits LPA-induced HCC cell invasion, demonstrating that MMP-9 is downstream of LPA1. Inhibition of phosphoinositide-3 kinase (PI3K) signaling or dominant-negative mutants of protein kinase Cδ and p38 mitogen-activated protein kinase (MAPK) abrogated LPA-induced MMP-9 expression and subsequent invasion. We thus demonstrate a mechanistic cascade of ATX-producing LPA with LPA activating LPA1 and inducing MMP-9 through coordinate activation of the PI3K and the p38 MPAK signaling cascades, providing novel biomarkers and potential therapeutic targets for HCC.

TNIP1, SLC15A4, ETS1, RasGRP3 and IKZF1 are associated with clinical features of systemic lupus erythematosus in a Chinese Han population.

Systemic lupus erythematosus (SLE) is an autoimmune disease with heterogeneous clinical manifestations influenced by genetic and environmental factors. Five novel susceptibility genes (TNIP1, SLC15A4, ETS1, RasGRP3 and IKZF1) for SLE have been identified in a recent genome-wide association study of a Chinese Han population. This study investigated their relationships with disease subphenotypes, including renal nephritis, photosensitivity, antinuclear antibody (ANA), age at diagnosis, malar rash, discoid rash, immunological disorder, oral ulcer, hematological disorder, neurological disorder, serositis, arthritis and vasculitis. Significant associations were found for the single nucleotide polymorphism rs10036748 of TNIP1 with photosensitivity (odds ratio (OR) = 0.87, p = 0.01) and vasculitis (OR = 1.18, p = 0.04); rs10847697 of SLC15A4 with discoid rash (OR = 1.18, p = 0.02); rs6590330 of ETS1 with SLE of age at diagnosis <20 years (OR = 1.24, p = 8.91 x 10(-5)); rs13385731 of RasGRP3 with malar rash (OR = 1.20, p = 0.01), discoid rash (OR = 0.78, p = 0.02) and ANA (OR = 0.72, p = 0.004); rs4917014 of IKZF1 with renal nephritis (OR = 1.13, p = 0.02) and malar rash (OR = 0.83, p = 0.00038), respectively. The study suggested that these susceptibility genes might not only play important roles in the development of SLE, but also contribute to the complex phenotypes of SLE.

Comprehensive clinical follow-up of late effects in childhood cancer survivors shows the need for early and well-timed intervention.

BACKGROUND: Due to recent advances in treatment, nearly 80% of childhood cancer patients become long-term survivors. Studies on the late effects of survivors are under way worldwide. However, data on Asian survivors remain limited. METHODS: Data on 241 survivors at the Long-term Follow-up Clinic in Severance Hospital, South Korea, were collected and late effects were confirmed by oncologists. RESULTS: The median follow-up from diagnosis was 7.8 years. Late effects were identified in 59.8% of survivors and 23.2% had two or more late effects. Grade 3 or higher late effects were present in 10.8%. The most common late effects involved endocrine system (29.0%). Late effects were present in 95.7% of brain tumor survivors and 36.0% of Wilms' tumor survivors. Chemotherapy, hematopoietic stem-cell transplantation and radiotherapy were significant factors associated with the number and severity of late effects (P < 0.05). Brain tumor survivors had more severe late effects (P < 0.001), whereas Wilms' tumor survivors had fewer and milder late effects (P < 0.05). CONCLUSION: The observation that over 50% of cancer survivors suffered from late effects during the short follow-up period and that a high frequency of endocrine late effects was present indicates the need for early and well-timed intervention of the survivors.

Validation of a simple method for measuring cranial deformities (plagiocephalometry).

Craniofacial measuring is essential for diagnosis or evaluation of growth and therapies. Skull deformities in children are mainly caused by craniosynostosis or by external pressure in positional skull deformations. Traditional anthropometry does not sufficiently analyze craniofacial shape. In computed tomography (CT) scanning, radiation loads are considerable. Both CT and magnetic resonance imaging (MRI) scanning require anaesthesia in children for accurate imaging, due to their long acquisition time. This makes CT and MRI unsuitable for long term follow-up of pediatric patients unless there is a compelling reason. Other noninvasive three-dimensional (3D) surface scanners still have limited practical use. van Vlimmeren et al presented plagiocephalometry (PCM) as a simple and versatile instrument to quantify skull deformities with high intrarater and interrater reliability, but no comparison was made with the actual skull shape. At the Erasmus University Medical Center Rotterdam, Sophia Children's Hospital PCM was compared to 3D-CT scanning in 21 children with craniosynostosis early in life. The PCM ring proved to fit closely to the skin with mean differences less than 1 mm (P < 0.05). The shape of the PCM ring was not significantly changed when taken off the head (P > 0.05). Finally, no significant differences are shown between measurements on the skull (CT-scan) and PCM ring off the head (P > 0.05). This study proves that PCM is a reliable method for analysis of skull deformities. The measurements are in agreement with 3D-CT scanning as golden standard. Although only 2-dimensional measurements are performed by PCM, the combination of simplicity, reliability, and validity make it a promising tool for daily practice.

Histone deacetylase inhibitor apicidin downregulates DNA methyltransferase 1 expression and induces repressive histone modifications via recruitment of corepressor complex to promoter region in human cervix cancer cells.

Dysregulation of DNA methyltransferase (DNMT)1 expression is associated with cellular transformation, and inhibition of DNMT1 exerts antitumorigenic effects. Here, we report that DNMT1 abnormally expressed in HeLa cells is downregulated by a histone deacetylase (HDAC) inhibitor apicidin, which is correlated with induction of repressive histone modifications on the promoter site. Apicidin selectively represses the expression of DNMT1 among DNMTs in HeLa cells, independent of cell cycle arrest at G0/G1. Furthermore, apicidin causes a significant reduction in the recruitment of RNA polymerase II into the promoter. Chromatin immunoprecipitation analysis shows that even though apicidin causes global hyperacetylation of histone H3 and H4, localized deacetylation of histone H3 and H4 occurs at the E2F binding site, which is accompanied by the recruitment of pRB and the replacement of P/CAF with HDAC1 into the sites. In addition, K4-trimethylated H3 on nucleosomes associated with the transcriptional start site is depleted following apicidin treatment, whereas repressive markers, K9- and K27-trimethylation of H3 are enriched on the site. The downregulation of DNMT1 expression seems to require de novo protein synthesis, because the apicidin effect is antagonized by cycloheximide treatment. Moreover, knock down of DNMT1 with siRNA induces the apoptosis of HeLa cells, indicating that downregulation of DNMT1 might be a good strategy for therapeutics of human cervix cancer. Collectively, our findings will provide a mechanistic rationale for the use of HDAC inhibitors in cancer therapeutics.

Safety and immunogenicity of a vaccine targeting human papillomavirus types 6, 11, 16 and 18: a randomized, placebo-controlled trial in 176 Korean subjects.

Human papillomavirus (HPV) is a major causative agent of anogenital warts and a necessary cause of cervical cancer. This report will serve to assess the safety and immunogenicity of quadrivalent (types 6, 11, 16, and 18) HPV L1 virus-like particle (VLP) vaccine in the Korean population. We performed a randomized, double-blind, placebo-controlled study in 176 volunteers aged 9-23 years. Using a 2:1 ratio for randomization, 117 women were assigned to quadrivalent HPV (20 mug type 6, 40 mug type 11, 40 mug type 16, and 20 mug type 18) vaccine and 59 women to placebo. Individuals received vaccine at day 1, month 2, and month 6 and provided blood samples for analysis at enrollment at month 7. Analyses were done as specified in the study protocol. Quadrivalent HPV vaccine was generally well tolerated, with no vaccine-related serious adverse experiences. Quadrivalent HPV vaccine induced seroconversion for each vaccine-related HPV type. At month 7, vaccine-induced type-specific antibody titer was high. In conclusion, administration of quadrivalent HPV VLP vaccine to Korean women aged 9-23 years was generally well tolerated and highly immunogenic.