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GATA3 polymorphisms were reported to be significantly associated with susceptibility of pediatric B-lineage acute lymphoblastic leukemia (ALL), by impacting on GATA3 expression. We noticed that ALL-related GATA3 polymorphism located around in the tissue-specific enhancer, and significantly associated with GATA3 expression. Although the regulatory network of GATA3 has been well reported in T cells, the functional status of GATA3 is poorly understood in B-ALL. We thus conducted genome-wide gene expression association analyses to reveal expression associated genes and pathways in nine independent B-ALL patient cohorts. In B-ALL patients, 173 candidates were identified to be significantly associated with GATA3 expression, including some reported GATA3-related genes (e.g., ITM2A) and well-known tumor-related genes (e.g., STAT4). Some of the candidates exhibit tissue-specific and subtype-specific association with GATA3. Through overexpression and down-regulation of GATA3 in leukemia cell lines, several reported and novel GATA3 regulated genes were validated. Moreover, association of GATA3 expression and its targets can be impacted by SNPs (e.g., rs4894953), which locate in the potential GATA3 binding motif. Our findings suggest that GATA3 may be involved in multiple tumor-related pathways (e.g., STAT/JAK pathway) in B-ALL to impact leukemogenesis through epigenetic regulation.

Programmed death ligand-1 (PD-L1), a promising antitumor target, has proven clinical value against many malignancies. However, the PD-L1 content of Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) and its correlation with clinical outcomes remain unclear. This study aimed to investigate PD-L1 expression in Xp11.2 RCC and to assess its prognostic value. Formalin-fixed paraffin-embedded specimens from 36 adult patients that were histologically confirmed (by fluorescence in situ hybridization) were subjected to immunohistochemical analysis. Of the 36 Xp11.2 RCC patients, 9 (25.0%) had tumors with positive PD-L1 expression and 27 (75.0%) had tumors with negative PD-L1 expression. Positive PD-L1 expression correlated with advanced tumor stage (P = 0.001), regional lymph node metastasis (P < 0.001), and distant metastasis (P < 0.001). A multivariate analysis identified positive PD-L1 expression was an independent adverse prognostic factor for both progression free survival (hazard ratio: 3.7, P = 0.018) and overall survival (hazard ratio: 4.5, P = 0.034). The median PFS and OS for the whole cohort were 13.0 months (95% confidence interval [CI], 9.4-16.6 months) and 36.0 months (95% CI, 23.9-48.1 months), respectively. Our findings suggest that positive PD-L1 expression is indicative of worse clinical outcome in Xp11.2 RCC. Further studies are needed to explore the potential efficacy of targeting PD-L1 in Xp11.2 RCC.

The distribution pattern of renal cell carcinoma (RCC) histological subtypes according to age, gender and tumor size has not been well illustrated in RCC patients living in fast-developing regions of China. We recruited 2941 patients with clear cell renal cell carcinoma (ccRCC), papillary renal cell carcinoma (PCC) or chromophobe from two hospitals in coastal China (2004-2012) consecutively and draw 538 American Chinese RCC patients' data with time matched from the Surveillance, Epidemiology, and End Results database. We found that compared with ccRCC patients, chromophobe patients were more likely to be female (OR: 2.538, 95% CI: 1.923-3.350), younger (OR for 51-60 years old: 0.686; OR for over 60 years old: 0.478; reference: age < 50) and to have a larger maximal diameter (Dmax) (OR for Dmax > 7 cm: 1.883; reference: Dmax ≤ 4 cm). Besides, in comparison with coastal Chinese patients, American Chinese individuals had lower Fuhrman grades ( P < 0.001) and had an onset age 10 years delay. In conclusion, we were the first to observe marked gender, age and tumor size differences in the proportional subtype distribution of RCCs in coastal Chinese patients, and also the first to compare coastal Chinese with American Chinese data., Competing Interests: CONFLICTS OF INTERESTS The author(s) indicated no potential conflicts of interest.

Recent studies showed that 2-deoxy-D-glucose (2-DG), a glucose analog with dual activity of inhibiting glycolysis and N-linked glycosylation, can be selectively taken up by cancer cells and be used as a potential chemo- and radio-sensitizer. Meanwhile, 2-DG can kill cancer cells under normoxia. However, its efficacy is limited by the high-dose induced systemic toxicity. Here, we showed that low-dose 2-DG could be used as a single agent to kill acute lymphoblastic leukemia (ALL) cells, and as a GC sensitizer to overcome GC resistance under normoxia. Addition of exogenous mannose, a sugar essential for N-linked glycosylation, rescued 2-DG-treated ALL cells, indicating that inhibition of N-linked glycosylation and induction of endoplasmic reticulum stress is the main mechanism for 2-DG to induce cell death and reverse GC resistance in ALL cells. These data provides new insight into the molecular mechanisms involved in GC resistance. More important, it indicates that 2-DG might be the promising drug for designing novel high efficiency and low toxic protocol for ALL patients.

Background: Nuclear receptors (NRs) are a class of transcription factors that regulate many cellular functions through manipulation of gene expression and also play important roles in tumorigenesis, proliferation, progression and prognosis in various kinds of cancers according to recent studies. This work aimed to determine the predictive ability of NRs in muscle-invasive bladder cancer (MIBC)., Patients and Methods: A total of 308 MIBC patients with complete clinicopathological and RNASeq data from The Cancer Genome Atlas (TCGA) cohort were collected for filtration. Genes showed clear correlations with overall survival (OS) and recurrence free survival (RFS) were further validated in 123 MIBC patients recruited consecutively from 2008 to 2012 in Fudan University Shanghai Cancer Center (FUSCC) cohort. Cox proportional hazards regression model and Kaplan-Meier plot were used to assess the relative factors., Results: In TCGA cohort, we found that high NR1H3 (HR=0.779, 95% CI: 0.634 - 0.957), NR2C1 (HR=0.673, 95% CI: 0.458 - 0.989) and NR2F6 (HR=0.750, 95% CI: 0.574 - 0.980) expressions were independent factors of favorable OS, while only low NR1H3 (log-rank test, P=0.0076) and NR2F6 (log-rank test, P=0.0395) expressions had the ability to predict poor prognosis for RFS. Further, in FUSCC validating cohort, we confirmed that low NR1H3 expression level was independent factor of poor OS (HR=1.295, 95% CI: 1.064 - 1.576) and it had the ability to predict poor RFS (log-rank test, P=0.0059)., Conclusions: Low NR1H3 expression level is an independent prognostic factor of poor OS, and can also predict worse RFS in MIBC patients. Our "TCGA filtrating and local database validating" model can help reveal more prognostic biomarkers and cast a new light in understanding certain gene function in MIBC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Thiopurines are widely used as anticancer and immunosuppressive agents. However, life-threatening myelotoxicity has been noticed and largely explained by genetic variations, including NUDT15 polymorphisms (e.g., rs116855232). In this study, we conduct a meta-analysis to investigate the impact of rs116855232 on thiopurines-induced myelotoxicity susceptibility (1752 patients from 7 independent cohorts), as well as on thiopurines intolerance dose (2745 patients from 13 cohorts). Variant allele of rs116855232 contributes 7.86-fold (P < 0.00001, 95% CI: 6.13-10.08) higher risk to develop leucopenia with high specificity (91.74%) and sensitivity (43.19%), and lower thiopurines intolerance dose (P < 0.00001). Through bioinformatics prediction, amino acid changes induced by genetic variants are considered to reduce the stability, and break an α helix of NUDT15, which is part of the thiopurine binding pocket. Additionally, we conduct an expression quantitative trait loci (eQTL) analysis for NUDT15, and find a promoter-located eQTL signal (rs554405994), which may act as a potential marker to predict thiopurines-induced myelotoxicity. In conclusion, genetic polymorphisms in NUDT15 are strongly associated with adverse drug reaction (ADR) of thiopurines, although more evidences are needed to determine values of all functional NUDT15 polymorphisms for clinical regimen, rs116855232 should be considered as a highly credible pharmacogenetic indicator for thiopurines using espcially is Asians.

N-myristoylation is the covalent attachment of myristic acid to the N terminus of proteins in eukaryotic cells. The matrix domain (MA) of HIV-1 Gag protein is N-myristoylated and plays an important role in virus budding. In screening for host factors that interact with HIV-1 MA, we found that heme oxygenase (HO-2) specifically binds the myristate moiety of Gag. HO-2 was also found to bind TRAM, an adaptor protein for Toll-like receptor 4 (TLR4), and thereby impact both virus replication and cellular inflammatory responses. A crystal structure revealed that HO-2 binds myristate via a hydrophobic channel adjacent to the heme-binding pocket. Inhibiting HO-2 expression, or blocking myristate binding with a heme analog, led to marked increases in virus production. HO-2 deficiency caused hyperresponsive TRAM-dependent TLR4 signaling and hypersensitivity to the TLR4 ligand lipopolysaccharide. Thus, HO-2 is a cellular myristate-binding protein that negatively regulates both virus replication and host inflammatory responses., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Long non-coding RNAs (lncRNAs) have been suggested to play important roles in the progression of many cancers such as bladder cancer. However, the detailed mechanism has not been fully understood. We have previously identified a collection of aberrantly expressed lncRNAs in bladder cancer using microarray gene profiling assay. In the current study, we aim to further explore the expression profile and the function of LOC572558, one of the most deregulated lncRNAs in bladder cancer. A large cohort of human bladder cancer tissue samples with benign controls, as well as established human bladder cancer cell lines, has been examined for the expression of LOC572558. The biological functions of LOC572558 were examined by CCK-8 assay, flow cytometry analysis, and wound healing and transwell assays. Using a high-throughput phospho-proteome array, we identified proteins that were ectopic phosphorylated in bladder cancer cells where LOC572558 expression was upregulated. We demonstrated that LOC572558 expression was markedly decreased in bladder cancer tissues and bladder cancer cell lines. Moreover, ectopic expression of LOC572558 inhibited cell proliferation and motility, induced S phase arrest of the cell cycle and promoted cell apoptosis in T24 and 5637 bladder cancer cell lines. We further verified that overexpression of LOC572558 was associated with dephosphorylation of AKT, MDM2 and phosphorylation of p53 protein. Our data clearly demonstrated that LOC572558 is a tumor suppressor and regulates the p53 signaling pathway in bladder cancer. Thus, it may serve as a promising new diagnostic marker and therapeutic target in bladder cancer., (Copyright © 2016. Published by Elsevier Ireland Ltd.)

Objectives: To examine whether serum adiponectin or leptin level has the ability to differentiate clear cell renal cell carcinoma (ccRCC) from other subtypes of renal cell carcinoma (RCC) in a Chinese population., Patients and Methods: We recruited 198 consecutive patients who were treated with radical or partial nephrectomy in our department from September 2011 to June 2013. Their histological types were all malignant, including clear cell, papillary, chromophobe and unclassified RCC. We also enrolled 86 people with no cancer or cancer-related diseases as normal controls. We measured patients' preoperative blood samples for plasma adiponectin and leptin concentrations using an enzyme-linked immunosorbent assay method. Statistical methods were used to analyze ccRCC and other subtypes as they relate to serum adiponectin/leptin level and other factors such as body mass index or visceral fat area., Results: In our database, normal controls had significantly higher circulating adiponectin (p < 0.001) and leptin levels (p < 0.001) than patients with RCC. Among the 198 RCC patients, 156 patients had ccRCC while 42 patients had other histological types. Serum adiponectin levels were lower in ccRCC patients than in non-clear-cell RCC patients (p = 0.004). However, the plasma leptin level was not differently distributed between ccRCC and non-ccRCC patients (p = 0.940). In multivariate analysis, we found that serum adiponectin level may be an independent predictor for discriminating ccRCC patients from others (p = 0.004). Furthermore, in the ccRCC subgroup, we observed that men with ccRCC had lower leptin (p < 0.001) and adiponectin (p = 0.002) levels, and diabetic patients had lower plasma adiponectin levels (p = 0.001)., Conclusions: Lower plasma adiponectin concentration was related to an increased incidence of ccRCC and may act as an independent predictor for ccRCC. Our study may help define the process from obesity to adipose tissue, to cytokines and finally to ccRCC.

Retroviral reverse transcriptase (RT) of Moloney murine leukemia virus (MoMLV) is expressed in the form of a large Gag-Pol precursor protein by suppression of translational termination in which the maximal efficiency of stop codon read-through depends on the interaction between MoMLV RT and peptidyl release factor 1 (eRF1). Here, we report the crystal structure of MoMLV RT in complex with eRF1. The MoMLV RT interacts with the C-terminal domain of eRF1 via its RNase H domain to sterically occlude the binding of peptidyl release factor 3 (eRF3) to eRF1. Promotion of read-through by MoMLV RNase H prevents nonsense-mediated mRNA decay (NMD) of mRNAs. Comparison of our structure with that of HIV RT explains why HIV RT cannot interact with eRF1. Our results provide a mechanistic view of how MoMLV manipulates the host translation termination machinery for the synthesis of its own proteins.

Background: The aim of this meta-analysis was to analyze the relationship of toxicities and clinical benefits of newly approved lenvatinib and sorafenib to thyroid cancer (TC) in patients., Materials and Methods: Three major medical databases, PubMed, EMBASE, and ISI web of science were systematically searched to identify all studies on lenvatinib and sorafenib in TC. A meta-analysis was performed to clarify the toxicities and clinical benefits of newly Food and Drug Administration (FDA) approved lenvatinib and sorafenib to thyroid cancer., Results: Ten studies (n = 749) were included which evaluated the toxicities and clinical benefits of newly FDA approved lenvatinib and sorafenib to thyroid cancer. 537 (71.7%) of the 749 patients bearing TC (radioiodine-refractory, differentiated thyroid cancer) clinical benefits from lenvatinib or sorafenib, and serious adverse events occurred in 430 (57.4%) of the 749 patients ([risk ratio (RR) = 1.27, 95% confidence interval (CI) = (1.05-1.53), P = 0.01]). While 31 (4.1%) of the 749 patients died due to various reasons, that mainly accounts for severe bleeding events and cardiac arrest. The clinical benefit is obvious compared to deaths ([RR = 17.06, 95% CI = (12.08-24.11), P < 0.001]). Subgroup analyses were then conducted according to cancer type (radioiodine-refractory thyroid cancer [RR-TC] and TC). We found that in treating RR-TC, the clinical benefits are close to toxicities. While in treating TC, the clinical benefits are better than toxicities. And we found that sorafenib and lenvatinib might be proper to deal with TC (benefits rate 79.7%) compared to RR-TC (benefits rate 69.5%), taking consider of toxicities., Conclusions: Lenvatinib and sorafenib are useful in the treatment of TC. Although, their toxicities remain high (57.4%) in the patients, the death rate is controlled (4.1%). Take consider of toxicities, lenvatinib, and sorafenib are more useful for TC compared to RR-TC.

Purpose: To assess the efficacy and safety of thulium laser versus standard transurethral resection of the prostate (TURP) for treating patients with benign prostatic obstruction., Methods: A systematic search of the electronic databases, including Medline, Embase, Web of Science, and The Cochrane Library, was performed up to February 1, 2014. The pooled estimates of demographic and clinical baseline characteristics, perioperative variables, complications, and postoperative efficacy including International Prostate Symptom Score (IPSS), quality of life (QoL), maximum flow rate (Qmax), and postvoid residual (PVR) were calculated., Results: Seven trials assessing thulium laser versus standard TURP were considered suitable for meta-analysis including four randomized controlled trials (RCTs) and three non-RCTs. Compared with TURP, although thulium laser prostatectomy (TmLRP) needed a longer operative time [weighted mean difference (WMD) 8.18 min; 95 % confidence interval (CI) 1.60-14.75; P = 0.01], patients having TmLRP might benefit from significantly less serum sodium decreased (-3.73 mmol/L; 95 % CI -4.41 to -3.05; P < 0.001), shorter time of catheterization (WMD -1.29 days; 95 % CI -1.95 to -0.63; P < 0.001), shorter length of hospital stay (WMD -1.83 days; 95 % CI -3.10 to -0.57; P = 0.005), and less transfusion (odds ratio 0.09; 95 % CI 0.02-0.41; P = 0.002). During the 1, 3, and, 12 months of postoperative follow-up, the procedures did not demonstrate a significant difference in IPSS, QoL, Qmax, and PVR., Conclusions: TmLRP had a similar efficacy to standard TURP in terms of IPSS, QoL, Qmax, and PVR, and offered several advantages over TURP in terms of blood transfusion, serum sodium decreased, catheterization time, and hospital stay, while TURP was superior in terms of operation duration. Well-designed multicentric/international RCTs with long-term follow-up are still needed.

Transmembrane protease serine 4 (TMPRSS4) is a type-II transmembrane serine protease that plays an important role in the migration of cancer cells. This study aimed to investigate both the expression of TMPRSS4 and its clinical significance in prostate cancer. The expression of TMPRSS4 was evaluated in 73 pairs of prostate cancer and adjacent non-cancerous tissues by immunohistochemistry. The level of TMPRSS4 in prostate cancer tissues was significantly higher than that in adjacent non-cancerous tissues. High TMPRSS4 expression was significantly associated with advanced TNM stage and LNM. No association between TMPRSS4 expression and progression-free survival was observed in all patients. Stratified analyses according to clinical features revealed that patients with low TMPRSS4 expression had poor prognosis compared with those with high TMPRSS4 expression in subjects not receiving neoadjuvant chemotherapy. In conclusion, TMPRSS4 showed abnormal expression in prostate cancer tissues. TMPRSS4 may be a potential prognostic biomarker for prostate cancer patients who did not undergo neoadjuvant chemotherapy.

Objective: To analyze mutations in a pedigree of familial hemophagocytic lymphohistiocytosis (FHLH) from Sichuan and provide genetic counseling for the family., Methods: Clinical data of a case with FHLH diagnosed at West China Second Hospital was retrospectively analyzed. Genomic DNA was extracted from peripheral blood samples of the proband and his family members. Eight candidate genes for primary HLH were amplified with PCR and analyzed by direct sequencing., Results: The proband was diagnosed as HLH based on clinical manifestations of recurrent fever for 2 months, hepatosplenomegaly, lymphadenopathy, pancytopenia, hyperferritinemia, and decreased fibrinogen and hemophagocytosis in bone marrow. Genetic testing for primary HLH was carried out considering the relapse of illness after hormone therapy for 8 weeks and the family history. The results of gene sequencing showed that the proband has carried compound heterozygous mutations in PRF1 gene (c.1349C> T in exon 3 and c.445G> A in exon 2). His father has carried a heterozygous mutation (c.445G> A in exon 2) and nonsense mutation (c.900C> T in exon 3), and his mother carried a heterozygous mutation (c.1349C> T in exon 3). Both c.1349C> T and c.445G> A have been previously reported as pathogenic mutations., Conclusion: The family has been diagnosed as familial HLH type 2 based on clinical and laboratory examinations and molecular genetic testing. Gene sequencing has indicated that is was a recessive type familial HLH.

Translational repression and mRNA degradation are two major mechanisms for post-transcriptional regulation of gene expression. The detailed relationship between these two processes is not yet well established. Zinc-finger antiviral protein (ZAP) inhibits the replication of certain viruses, including human immunodeficiency virus 1, by binding directly to specific viral mRNAs and recruiting cellular mRNA degradation machinery to degrade the target mRNA. Here, we report that ZAP also inhibits the translation of target mRNAs by interfering with the interaction between translational initiation factors eIF4G and eIF4A. Furthermore, we provide evidence that translational repression is required for mRNA degradation and that blocking the degradation of target mRNAs does not affect ZAP-mediated translational repression. We conclude that ZAP can both repress translation and promote degradation of target mRNA, and that translational repression precedes and is required for mRNA degradation.

Background: Little is known about the risks of bone fractures in elderly patients with mental disorders in China., Aim: Assess the bone mineral density (BMD) of elderly patients with mental disorders in China and identify factors that are associated with low BMD, osteopenia and osteoporosis., Methods: One hundred and two psychiatric inpatients 60 years of age or older (including patients with schizophrenia, depression, bipolar disorder and dementia) were randomly selected from patients in the geriatric wards of the Third People's Hospital of Huzhou. Detailed demographic, clinical and biometric data were obtained and the BMD of the lumbar spine was assessed using standard dual energy X-ray absorptiometry (DXA) procedures. Based on WHO criteria, individuals with BMD 1 to 2.5 standard deviations below the mean value for healthy young adults were diagnosed as osteopenia and those with BMD values 2.5 or more standard deviations below the mean value were diagnosed as osteoporosis., Results: The prevalence of osteopenia was 33.3% (95% CI, 24.4%-43.2%) and the prevalence of osteoporosis was 35.3% (26.0%-45.2%) but none of these patients - even the five patients who had had non-traumatic fractures - had ever been treated for these conditions. The prevalence of osteoporosis in females was 10-fold that in males (53% versus 5%). BMD decreased with age and increased with increasing body mass index (a reflection of nutritional status). The prevalence of osteoporosis was much higher in patients with a diagnosis of depression (58%) than in those with schizophrenia (33%), Alzheimer's disease (30%) or bipolar disorder (13%). Regression analyses found that low BMD and the combined category of osteopenia and osteoporosis were both independently associated with female gender, increasing age, decreasing body mass index, and a diagnosis of depression. BMD and osteoporosis were not significantly associated with regular use of antipsychotic medication., Conclusion: Osteopenia and osteoporosis are common conditions in elderly patients with mental disorders that can seriously affect their quality of life but they often go undiagnosed and untreated. Long-term prospective studies are needed to clarify the relative importance of nutritional status, activity level, medication usage, and other factors in the causal pathways that connect mental illnesses to BMD.

The zinc-finger antiviral protein (ZAP) was originally identified as a host factor that inhibits the replication of Moloney murine leukemia virus. Here we report that ZAP inhibits HIV-1 infection by promoting the degradation of specific viral mRNAs. Overexpression of ZAP rendered cells resistant to HIV-1 infection in a ZAP expression level-dependent manner, whereas depletion of endogenous ZAP enhanced HIV-1 infection. Both human and rat ZAP inhibited the propagation of replication-competent HIV-1. ZAP specifically targeted the multiply spliced but not unspliced or singly spliced HIV-1 mRNAs for degradation. We provide evidence indicating that ZAP selectively recruits cellular poly(A)-specific ribonuclease (PARN) to shorten the poly(A) tail of target viral mRNA and recruits the RNA exosome to degrade the RNA body from the 3' end. In addition, ZAP recruits cellular decapping complex through its cofactor RNA helicase p72 to initiate degradation of the target viral mRNA from the 5' end. Depletion of each of these mRNA degradation enzymes reduced ZAP's activity. Our results indicate that ZAP inhibits HIV-1 by recruiting both the 5' and 3' mRNA degradation machinery to specifically promote the degradation of multiply spliced HIV-1 mRNAs.

Study was carried out for the removal of hazardous organic compound from aqueous solution by using water/perfluorodecalin loaded ozone two-phase system. p-Chloronitrobenzene was used as hazardous organics to examine the efficiency of the two-phase ozonation system. Effects of initial pH in water, stirring speed, initial molar ratio of O(3)/p-chloronitrobenzene (M), and free radical scavenger on the removal rate of p-chloronitrobenzene were investigated respectively. It was revealed that ozone had low decomposed rate coefficient k = 0.0035 min(-1) and solubility of 61.94 mg/L at 25°C in perfluorocarbon. In contrast to pH 2.0, higher level of pH (8.0) in water increased the removal rate of p-chloronitrobenzene in water/perfluorocarbon two-phase ozonation system. Removal rate of p-chloronitrobenzene was increased with the elevation of initial M value in water/perfluorocarbon two-phase ozonation system. Stirring speed was needed to control with proper level of speed in water/perfluorocarbon two-phase system. Compared to the conventional gas/water ozonation system, NaHCO(3) (20 mmol/L) had no obvious negative effect on the p-chloronitrobenzene degradation in water/perfluorocarbon ozonation system. Oxidation efficiency of ozonation in water/perfluorocarbon system was superior to that of in conventional gas/water system.

The zinc-finger antiviral protein (ZAP) is a host factor that specifically inhibits the replication of certain viruses by eliminating viral mRNAs in the cytoplasm. In previous studies, we demonstrated that ZAP directly binds to the viral mRNAs and recruits the RNA exosome to degrade the target RNA. In this article, we provide evidence that a DEXH box RNA helicase, DHX30, is required for optimal antiviral activity of ZAP. Pull-down and co-immunoprecipitation assays demonstrated that DHX30 and ZAP interacted with each other via their N terminal domains. Downregulation of DHX30 with shRNAs reduced ZAP's antiviral activity. These data implicate that DHX30 is a cellular factor involved in the antiviral function of ZAP.

The aim of this study was to determine the incidence of prostate cancer in patients with extramammary Paget's disease (EMPD). All cases of EMPD diagnosed between 1992 and 2007 in Shanghai Cancer Hospital were collected and analyzed for the incidence of prostate cancer. The median follow-up was 78 months. In total, 38 cases of invasive and 10 cases of in situ EMPD had been registered. A second malignancy was found in 28.9% (11/38) of patients with invasive EMPD and in 30% (3/10) of patients with in situ EMPD. Patients had an increased risk of developing a second cancer compared with the general population (standardized incidence ratio: 1.7; 95% confidence interval 1.2-2.4). Sixteen patients had serum prostate-specific antigen (PSA) level above 4 ng/mL; five developed prostate cancer, three of them with PSA levels beyond 100 ng/mL. The incidence of prostate cancer is 10.4% in this patient group. Patients with EMPD were more likely to have prostate cancer than the general population. Although the prognosis of EMPD is fairly good, a thorough search for a second tumor is recommended., (© 2010 The Authors. Journal Compilation © 2010 APMIS.)

The t(5;17)/NPM-RARalpha is the second variant chromosomal translocation in acute promyelocytic leukemia (APL) to be characterized and also the second most plentiful variant translocation. So far, there is a lack of information on the effectiveness of arsenic trioxide (ATO) in relapsed APL with variant RARalpha chimera including t(5;17)/NPM-RARalpha. We report here a long-term survived APL patient with variant NPM-RARalpha fusion who relapsed four times and each time responded well to ATO or ATO-based re-induction therapy. The patient had received a total of more than 3,500 mg of ATO, but showed no obvious arsenic-related toxicities. This case illustrates the long-term efficiency and safety of ATO-based therapy not only in newly diagnosed APL, but also in relapsed APL including those with variant translocations.

Pollutant washoff loads from an expressway in Shanghai, China were investigated during a 1-year study program. The median washoff load during an rainfall event for total solids, chemical oxygen demand, total nitrogen and total phosphorus were 4,389.8, 2,123.0, 47.6 and 1.6 mg/m(2), respectively. Through principal factor analysis, three factors that represent the influence of pollutant source availability, rainfall volume and rainfall intensity account for 89% variance of the monitoring data. The result of multiple regression analysis reveals that antecedent dry period significantly influences the washoff load, while peak rainfall intensity and runoff volume may have some influence, which correlates well with the principal factor analysis results.

To explore novel effective drugs for the treatment of Alzheimer's disease (AD), a series of dual inhibitors of acetylcholineterase (AChE) and beta-secretase (BACE-1) were designed based on the multi-target-directed ligands strategy. Among them, inhibitor 28 exhibited good dual potency in enzyme inhibitory potency assay (BACE-1: IC(50)=0.567 microM; AChE: IC(50)=1.83 microM), and also showed excellent inhibitory effects on Abeta production of APP transfected HEK293 cells (IC(50)=98.7 nM) and mild protective effect against hydrogen peroxide (H(2)O(2))-induced PC12 cell injury. Encouragingly, intracerebroventricular injection of 28 into amyloid precursor protein (APP) transgenic mice caused a 29% reduction of Abeta(1-40) production. Therefore, 28 was demonstrated as a good lead compound for the further study and more importantly, the strategy of AChE and BACE-1 dual inhibitors might be a promising direction for developing novel drugs for AD patients.