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Copyright of Scientific Journal of Agricultural Sciences (SJAS) is the property of Beni Suef University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Scientific Journal of Agricultural Sciences (SJAS) is the property of Beni Suef University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The preparation and characterization of ultrafine superparamagnetic Fe3O4 (magnetite) nanoparticles and their composites with the PMMA polymer matrix are described. The cubic structure with space group (Fd 3 ¯ m) of the nanofiller particle Fe3O4 is revealed by x-ray diffraction (XRD) studies. Scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) were used to examine the microstructure and elemental compositions of PMMA-Fe3O4 polymer composites. The interaction of the filler particles with the characteristic functional group of the polymer PMMA was detected using Fourier-transform infrared spectroscopy (FTIR). UV-spectroscopy studies revealed that PMMA-Fe3O4 nanocomposite films have tunable energy band gap properties, with the band gap decreasing as the magnetite filler particles (Fe3O4) in the polymer matrix increased. Magnetic measurements revealed the superparamagnetic nature of the Fe3O4 nanoparticles at room temperature, which was also found to be present in the nanocomposites. These nanocomposites were found to be ferrimagnetic at low temperatures (5 K) similar to that of the nanoparticles (Fe3O4). The blocking temperature (TB) of the nanocomposites was found to increase with the superparamagnetic Fe3O4 nanoparticle content, while the saturation magnetization (Ms) of the polymer nanocomposites decreased consistently. The Ms value was also estimated using TGA data, and the Ms values of different nanoparticles and nanocomposites calculated via TGA correlates with those determined from VSM analysis. [ABSTRACT FROM AUTHOR]

Zinc oxide nanoparticles (ZnO-NPs) have widespread applications in various industries and cosmetics that raise concerns about their hazards to the environment. Eco-toxicological data show that nanoscale zinc oxide has harmful impacts on both aquatic species and human health. The co-precipitation method was followed to synthesize ZnO-NPs and X-ray diffraction (XRD) technique and scanning electron microscope (SEM) were used for characterization. The acute toxicity at 96h was determined by using Bighead carp as a model fish after the exposure to 11 various concentrations (2-50mg/L) of ZnO-NPs. The mean 96-h LC50 was measured as 22.24mg/L. Bighead carp showed different behavioral changes that lead to death during acute toxicity tests. Oxidative stress in terms of lipid peroxidation (LPO) and superoxide dismutase (SOD) was determined in fish gills and liver after chronic exposure to ZnO-NPs for 90 days and sampling was done at 15, 30, 45, 60, 75 and 90-day intervals. Significant alterations in SOD and LPO levels were determined in tissues of the liver and gills as compared to the control group. We conclude that induced toxicity mechanism of ZnO-NPs suspension in freshwater environments may be due to elevated oxidative stress. [ABSTRACT FROM AUTHOR]

Zinc oxide nanoparticles (ZnO-NPs) have widespread applications in various industries and cosmetics that raise concerns about their hazards to the environment. Eco-toxicological data show that nanoscale zinc oxide has harmful impacts on both aquatic species and human health. The co-precipitation method was followed to synthesize ZnO-NPs and X-ray diffraction (XRD) technique and scanning electron microscope (SEM) were used for characterization. The acute toxicity at 96h was determined by using Bighead carp as a model fish after the exposure to 11 various concentrations (2-50mg/L) of ZnO-NPs. The mean 96-h LC50 was measured as 22.24mg/L. Bighead carp showed different behavioral changes that lead to death during acute toxicity tests. Oxidative stress in terms of lipid peroxidation (LPO) and superoxide dismutase (SOD) was determined in fish gills and liver after chronic exposure to ZnO-NPs for 90 days and sampling was done at 15, 30, 45, 60, 75 and 90-day intervals. Significant alterations in SOD and LPO levels were determined in tissues of the liver and gills as compared to the control group. We conclude that induced toxicity mechanism of ZnO-NPs suspension in freshwater environments may be due to elevated oxidative stress. [ABSTRACT FROM AUTHOR]

Copyright of Annals of Agricultural Science Moshtohor is the property of Egyptian National Agricultural Library (ENAL) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Annals of Agricultural Science Moshtohor is the property of Egyptian National Agricultural Library (ENAL) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Annals of Agricultural Science Moshtohor is the property of Egyptian National Agricultural Library (ENAL) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Annals of Agricultural Science Moshtohor is the property of Egyptian National Agricultural Library (ENAL) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Annals of Agricultural Science Moshtohor is the property of Egyptian National Agricultural Library (ENAL) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The modified Hehner's test (MHT) was applied to detect the formalin in experimentally contaminated and collected commercial cheeses and fish. The spectrophotometric method was adapted to determine the formalin in cheeses and fish samples. The principle of test modification was a complete homogenization and dilution of the examined cheeses and fish samples. By two methods, the incidences of formalin in the market soft and Ras cheeses samples were 31.66 and 3.33%, respectively. Formalin was not detected in the examined market fish samples by MHT, and its concentration by the spectrophotometric method was less than 1 µg/g. The findings of the study indicated that the results obtained by both MHT and spectrophotometric methods were comparable. The applicability of the MHT in different food matrices might mean it has potential as a standard technique with high sensitivity up to 0.001%. (A): Prepared Ras cheese homogenate; (B): Positive and negative modified Hehner's test in the examined Ras cheese samples with different formalin concentrations; (C): Positive and negative modified Hehner's test in the examined soft cheese samples with different formalin concentrations; (D): Negative modified Hehner's test in the examined fish flesh samples with 0.001% formalin concentration; (E): Positive modified Hehner's test in the examined fish flesh samples with 0.1% formalin concentration; (F): Positive modified Hehner's test in the examined fish wash samples with 0.01% formalin concentration [ABSTRACT FROM AUTHOR]

Copyright of Annals of Agricultural Science Moshtohor is the property of Egyptian National Agricultural Library (ENAL) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Plant Production is the property of Egyptian National Agricultural Library (ENAL) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Plant Production is the property of Egyptian National Agricultural Library (ENAL) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The thin film of poly(methyl methacrylate) (PMMA) has been widely studied as host in a polymer electrolyte system due to its good mechanical stability towards lithium electrode. However, the brittle property of this film creates additional resistance for the ionic conduction. The addition of ionic liquid (IL) has been noticed to improve the brittleness of the film. In addition, its ionic conductivity can also be enhanced, but no free standing film can be obtained when higher amount of IL was added. Therefore, in this study, 1-methyl-3-pentamethyldisiloxymethylimidazolium bis(trifluoromethylsulfonyl)imide,[(SiOSi)CCim][NTf], was incarcerated during free radical polymerization of MMA. Interestingly, this newly synthesized PMMA (PMMA) gives a flexible and transparent film with ionic conductivity of ∼10 S/cm at room temperature. The structural properties of this PMMA were further investigated using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and optical microscope (OM). [ABSTRACT FROM AUTHOR]

Coronary revascularisation has been a topic of debate for over three decades in patients undergoing high-risk non-cardiac surgery. The paradigm shifted from routine coronary angiography toward stress test guided decision-making based on larger randomised trials. However, this paradigm is challenged by relatively newer data where routine coronary angiography and revascularisation is shown to improve perioperative cardiovascular outcomes. We review major studies performed over a long period including more contemporary data with regard to the 2014 American College of Cardiology/American Heart Association as well as 2014 European Society of Cardiology guideline on perioperative cardiovascular evaluation of patients undergoing non-cardiac surgery. [ABSTRACT FROM AUTHOR]

The detection of promoter region hypermethylation and transcriptional silencing has facilitated the identification of candidate renal cell carcinoma (RCC) tumour suppressor genes (TSGs). We have used a genome-wide strategy (methylated DNA immunoprecipitation (MeDIP) and whole-genome array analysis in combination with high-density expression array analysis) to identify genes that are frequently methylated and silenced in RCC. MeDIP analysis on 9 RCC tumours and 3 non-malignant normal kidney tissue samples was performed, and an initial shortlist of 56 candidate genes that were methylated by array analysis was further investigated; 9 genes were confirmed to show frequent promoter region methylation in primary RCC tumour samples (KLHL35 (39%), QPCT (19%), SCUBE3 (19%), ZSCAN18 (32%), CCDC8 (35%), FBN2 (34%), ATP5G2 (36%), PCDH8 (58%) and CORO6 (22%)). RNAi knockdown for KLHL35, QPCT, SCUBE3, ZSCAN18, CCDC8 and FBN2 resulted in an anchorage-independent growth advantage. Tumour methylation of SCUBE3 was associated with a significantly increased risk of cancer death or relapse (P=0.0046). The identification of candidate epigenetically inactivated RCC TSGs provides new insights into renal tumourigenesis. [ABSTRACT FROM AUTHOR]

We have recently described the N-terminal RAS association domain family of genes, RASSF7-10. Previously, we cloned the N-terminal RASSF10 gene and demonstrated frequent methylation of the associated 5′-CpG island in acute lymphoblastic leukemia. To characterize RASSF10 gene expression, we demonstrate that in developing Xenopus embryos, RASSF10 shows a very striking pattern in the rhombencephalon (hind brain). It is also expressed in other parts of the brain and other organs. Due to the well-defined expression pattern in the brain of Xenopus embryos, we analyzed the methylation status of the RASSF10-associated 5′-CpG island in astrocytic gliomas. RASSF10 was frequently methylated in WHO grade II-III astrocytomas and WHO grade IV primary glioblastomas (67.5%), but was unmethylated in grade I astrocytomas and in DNA from age matched control brain samples. RASSF10 gene expression both at the mRNA and protein levels could be switched back on in methylated glioma cell lines after treatment with 5-aza-2′-deoxycytidine. In secondary glioblastomas (sGBM), RASSF10 methylation was an independent prognostic factor associated with worst progression-free survival and overall survival and occurred at an early stage in their development. In cell culture experiments, overexpression of RASSF10 mediated a reduction in the colony forming ability of two RASSF10-methylated glioma cell lines. Conversely, RNAi-mediated knockdown of RASSF10-stimulated anchorage-independent growth of U87 glioma cells, increased their viability and caused an increase in the cells' proliferative ability. We generated and characterized a RASSF10-specific antibody and demonstrated for the first time that RASSF10 subcellular localization is cell-cycle dependent with RASSF10 colocalizing to centrosomes and associated microtubules during mitosis. This is the first report demonstrating that RASSF10 can act as a tumor suppressor gene and is frequently methylated in gliomas and can potentially be developed into a prognostic marker for sGBM. [ABSTRACT FROM AUTHOR]

The neuronal repellent SLIT2 is repressed in a number of cancer types primarily through promoter hypermethylation. SLIT2, however, has not been studied in prostate cancer. Through genome-wide location analysis we identified SLIT2 as a target of polycomb group (PcG) protein EZH2. The EZH2-containing polycomb repressive complexes bound to the SLIT2 promoter inhibiting its expression. SLIT2 was downregulated in a majority of metastatic prostate tumors, showing a negative correlation with EZH2. This repressed expression could be restored by methylation inhibitors or EZH2-suppressing compounds. In addition, a low level of SLIT2 expression was associated with aggressive prostate, breast and lung cancers. Functional assays showed that SLIT2 inhibited prostate cancer cell proliferation and invasion. Thus, this study showed for the first time the epigenetic silencing of SLIT2 in prostate tumors, and supported SLIT2 as a potential biomarker for aggressive solid tumors. Importantly, PcG-mediated repression may serve as a precursor for the silencing of SLIT2 by DNA methylation in cancer. [ABSTRACT FROM AUTHOR]

The Ras-assocation domain family (RASSF) of tumor suppressor proteins until recently contained six proteins named RASSF1–6. Recently, four novel family members, RASSF7–10, have been identified by homology searches for RA-domain-containing proteins. These additional RASSF members are divergent and structurally distinct from RASSF1–6, containing an N-terminal RA domain and lacking the Sav/RASSF/Hpo (SARAH) domain. Here, we show that RASSF8 is ubiquitously expressed throughout the murine embryo and in normal human adult tissues. Functionally, RNAi-mediated knockdown of RASSF8 in non-small-cell lung cancer (NSCLC) cell lines, increased anchorage-independent growth in soft agar and enhanced tumor growth in severe combined immunodeficiency (SCID) mice. Furthermore, EdU staining of RASSF8-depleted cells showed growth suppression in a manner dependent on contact inhibition. We show that endogenous RASSF8 is not only found in the nucleus, but is also membrane associated at sites of cell–cell adhesion, co-localizing with the adherens junction (AJ) component β-catenin and binding to E-cadherin. Following RASSF8 depletion in two different lung cancer cell lines using alternative small interfering RNA (siRNA) sequences, we show that AJs are destabilized and E-cadherin is lost from the cell membrane. The AJ components β-catenin and p65 are also lost from sites of cell–cell contact and are relocalized to the nucleus with a concomitant increase in β-catenin-dependent and nuclear factor-κB (NF-κB)-dependent signaling following RASSF8 depletion. RASSF8 may also be required to maintain actin -cytoskeletal organization since immunofluorescence analysis shows a striking disorganization of the actin- cytoskeleton following RASSF8 depletion. Accordingly, scratch wound healing studies show increased cellular migration in RASSF8-deficient cells. These results implicate RASSF8 as a tumor suppressor gene that is essential for maintaining AJs function in epithelial cells and have a role in epithelial cell migration. [ABSTRACT FROM AUTHOR]

Promoter region hyermethylation and transcriptional silencing is a frequent cause of tumour suppressor gene (TSG) inactivation in many types of human cancers. Functional epigenetic studies, in which gene expression is induced by treatment with demethylating agents, may identify novel genes with tumour-specific methylation. We used high-density gene expression microarrays in a functional epigenetic study of 11 renal cell carcinoma (RCC) cell lines. Twenty-eight genes were then selected for analysis of promoter methylation status in cell lines and primary RCC. Eight genes (BNC1, PDLIM4, RPRM, CST6, SFRP1, GREM1, COL14A1 and COL15A1) showed frequent (>30% of RCC tested) tumour-specific promoter region methylation. Hypermethylation was associated with transcriptional silencing. Re-expression of BNC1, CST6, RPRM and SFRP1 suppressed the growth of RCC cell lines and RNA interference knock-down of BNC1, SFRP1 and COL14A1 increased the growth of RCC cell lines. Methylation of BNC1 or COL14A1 was associated with a poorer prognosis independent of tumour size, stage or grade. The identification of these epigenetically inactivated candidate RCC TSGs can provide insights into renal tumourigenesis and a basis for developing novel therapies and biomarkers for prognosis and detection. [ABSTRACT FROM AUTHOR]

RASSF2 is a tumour suppressor that in common with the rest of the RASSF family contains Ras association and SARAH domains. We identified the proapoptotic kinases, MST1 and MST2, as the most significant binding partners of RASSF2, confirmed the interactions at endogenous levels and showed that RASSF2 immunoprecipitates active MST1/2. We then showed that RASSF2 can be phosphorylated by a co-immunoprecipitating kinase that is likely to be MST1/2. Furthermore, we showed that RASSF2 and MST2 do indeed colocalize, but whereas RASSF2 alone is nuclear, the presence of MST1 or MST2 results in colocalization in the cytoplasm. Expression of RASSF2 (stably in MCF7 or transiently in HEK-293) increases MST2 levels and knockdown of RASSF2 in HEK-293 cells reduces MST2 levels, in addition colorectal tumour cell lines and primary tumours with low RASSF2 levels show decreased MST2 protein levels. This is likely to be mediated by RASSF2-dependent protection of MST2 against proteolytic degradation. Our findings suggest that MST2 and RASSF2 form an active complex in vivo, in which RASSF2 is maintained in a phosphorylated state and protects MST2 from degradation and turnover. Thus, we propose that the frequent loss of RASSF2 in tumours results in the destablization of MST2 and thus decreased apoptotic potential.Oncogene (2009) 28, 2988–2998; doi:10.1038/onc.2009.152; published online 15 June 2009 [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine the prevalence of rheumatic heart disease (RHD) among school children in urban and semiurban areas of Lahore, Pakistan. METHODS: A cross-sectional survey of school children aged 5-15 years from 70 schools of urban and semiurban Lahore was carried out by a team of cardiologists. Children were screened by clinical examination and diagnosis confirmed by echocardiography. Sociodemographic data were also collected. RESULTS: Of 24 980 children screened, 986 (3.9%) had a confirmed cardiac lesion; 546 had RHD, 440 had congenital heart disease. The prevalence of RHD was 21.9/1000 children screened (95% CI 20.1 to 23.7). Their mean (SD) age was 10.7 (2.6) years and the female:male ratio was 1.6:1. Most (92.5%) were unaware of the diagnosis and less than 2% were taking rheumatic prophylaxis. All children belonged to a low socioeconomic group and 67% were undernourished. CONCLUSION: The prevalence of RHD in the urban school population of Lahore is among the highest in the world. The younger age of onset is a special feature and most are unaware of the diagnosis, and hence not receiving life-saving secondary prophylaxis. [ABSTRACT FROM AUTHOR]

The article presents a study which aims to determine the effect of enzyme supplemented high fibre sunflower meal on performance of broiler birds. The study used sunflower meals (SFM) supplemented with commercial enzymes Grindazym and from National Institute of Biotechnology and Genetic Engineering (NIBGE) which were fed to 320-day old Hubbard broiler chicks. The study suggested that enzyme supplementation can help improve the digestion of fiber contents of SFM and increases the bioavailabity of metabolized energy. The study concluded that enzyme supplemented SFM is safe to use as bird feed and it does not compromise the performance of the birds and reduces the cost of feed production.

Attenuated total reflectance–Fourier transformed infrared spectroscopy measurement is employed to study the interactions between the components of 30% methyl-grafted natural rubber (MG30), lithium trifluromethanesulfonate (LiCF3SO3 or LiTF), and propylene carbonate (PC). Vibrational spectra data of LiTF reveals that the νs(SO3) at 1,045 cm−1, δs(CF3) at 777 cm−1, and C=O stretching mode at 1,728 cm−1 for MG30 have shifted to lower wave numbers in MG30–LiTF complexes indicating that complexation has occurred between MG30 and LiTF. The solvation of lithium ion is manifested in Li+ ← O=C interaction as shown by the downshifting and upshifting of C=O mode at 1,788 to 1,775 cm−1 and νas(SO3) at 1,250 to 1258 cm−1, respectively, in LiTF–PC electrolytes. There is no experimental evidence of the interaction between MG30 and PC. Competition between MG30 and PC on associating with lithium ion is studied, and the studies show that the interaction between MG30–LiTF is stronger than that of the PC–LiTF in plasticized polymer–salt complexes. The effect of PC on the ionic conductivity of the MG30–LiTF system is explained in terms of the polymer, plasticizer, and salt interactions. The temperature dependence of conductivity of the polymer films obeys the Vogel–Tamman–Fulcher relation. Values of conductivity and activation energy of the MG30-based polymer electrolyte systems are presented and discussed. [ABSTRACT FROM AUTHOR]

RASSF2 is a recently identified member of a class of novel tumour suppressor genes, all containing a ras-association domain. RASSF2 resides at 20p13, a region frequently lost in human cancers. In this report we investigated methylation status of the RASSF2 promoter CpG island in a series of breast, ovarian and non-small cell lung cancers (NSCLC). RASSF2 was frequently methylated in breast tumour cell lines (65%, 13/20) and in primary breast tumours (38%, 15/40). RASSF2 expression could be switched back on in methylated breast tumour cell lines after treatment with 5′-aza-2′deoxycytidine. RASSF2 was also frequently methylated in NSCLC tumours (44%, (22/50). The small number of corresponding normal breast and lung tissue DNA samples analysed were unmethylated. We also did not detect RASSF2 methylation in ovarian tumours (0/17). Furthermore no mutations were found in the coding region of RASSF2 in these ovarian tumours. We identified a highly conserved putative bipartite nuclear localization signal (NLS) and demonstrated that endogenous RASSF2 localized to the nucleus. Mutation of the putative NLS abolished the nuclear localization. RASSF2 suppressed breast tumour cell growth in vitro and in vivo, while the ability of NLS-mutant RASSF2 to suppress growth was much diminished. Hence we demonstrate that RASSF2 has a functional NLS that is important for its tumour suppressor gene function. Our data from this and a previous report indicate that RASSF2 is frequently methylated in colorectal, breast and NSCLC tumours. We have identified RASSF2 as a novel methylation marker for multiple malignancies and it has the potential to be developed into a valuable marker for screening several cancers in parallel using promoter hypermethylation profiles.Oncogene (2008) 27, 1805–1811; doi:10.1038/sj.onc.1210805; published online 24 September 2007 [ABSTRACT FROM AUTHOR]

Promoter region hypermethylation and transcriptional silencing is a frequent cause of tumour suppressor gene (TSG) inactivation in many human cancers. Previously, to identify candidate epigenetically inactivated TSGs in renal cell carcinoma (RCC), we monitored changes in gene expression in four RCC cell lines after treatment with the demethylating agent 5-azacytidine. This enabled us to identify HAI-2/SPINT2 as a novel epigenetically inactivated candidate RCC TSG. To identify further candidate TSGs, we undertook bioinformatic and molecular genetic evaluation of a further 60 genes differentially expressed after demethylation. In addition to HAI-2/SPINT2, four genes (PLAU, CDH1, IGFB3 and MT1G) had previously been shown to undergo promoter methylation in RCC. After bioinformatic prioritisation, expression and/or methylation analysis of RCC cell lines+/-primary tumours was performed for 34 genes. KRT19 and CXCL16 were methylated in RCC cell lines and primary RCC; however, 22 genes were differentially expressed after demethylation but did not show primary tumour-specific methylation (methylated in normal tissue (n=1); methylated only in RCC cell lines (n=9) and not methylated in RCC cell lines (n=12)). Re-expression of CXCL16 reduced growth of an RCC cell line in vitro. In a summary, a functional epigenomic analysis of four RCC cell lines using microarrays representing 11 000 human genes yielded both known and novel candidate TSGs epigenetically inactivated in RCC, suggesting that this is valid strategy for the identification of novel TSGs and biomarkers. [ABSTRACT FROM AUTHOR]

Deletions of the 3p21.3 region are a frequent and early event in the formation of lung, breast, kidney and other cancers. Intense investigation of allelic losses and the discovery of overlapping homozygous deletions in lung and breast tumour-cell lines have defined a minimal critical 120 kb deletion region containing eight genes and likely to harbor one or more tumour-suppressor genes (TSGs). The candidate genes are HYAL2, FUS1, Ras-associated factor 1 (RASSF1), BLU/ZMYND10, NPR2L, 101F6, PL6 and CACNA2D2. Recent research indicates that several of these genes can suppress the growth of lung and other tumour cells. Furthermore, some genes (RASSF1A and BLU/ZMYND10) are very frequently inactivated by non-classical mechanisms such as promoter hypermethylation resulting in loss of expression. These data indicate that the 120 kb critical deletion region at 3p21.3 may represent a TSG cluster with preferential inactivation of particular genes depending on tumour type. The eight genes within this region and their potential role in cancer will be the focus of this review.Oncogene (2007) 26, 7283–7301; doi:10.1038/sj.onc.1210547; published online 28 May 2007 [ABSTRACT FROM AUTHOR]

RASSF family proteins are tumor suppressors that are frequently downregulated during the development of human cancer. The best-characterized member of the family is RASSF1A, which is downregulated by promoter methylation in 40–90% of primary human tumors. We now identify and characterize a novel member of the RASSF family, RASSF6. Like the other family members, RASSF6 possesses a Ras Association domain and binds activated Ras. Exogenous expression of RASSF6 promoted apoptosis, synergized with activated K-Ras to induce cell death and inhibited the survival of specific tumor cell lines. Suppression of RASSF6 enhanced the tumorigenic phenotype of a human lung tumor cell line. Furthermore, RASSF6 is often downregulated in primary human tumors. RASSF6 shares some similar overall properties as other RASSF proteins. However, there are significant differences in biological activity between RASSF6 and other family members including a discrete tissue expression profile, cell killing specificity and impact on signaling pathways. Moreover, RASSF6 may play a role in dictating the degree of inflammatory response to the respiratory syncytial virus. Thus, RASSF6 is a novel RASSF family member that demonstrates the properties of a Ras effector and tumor suppressor but exhibits biological properties that are unique and distinct from those of other family members.Oncogene (2007) 26, 6203–6211; doi:10.1038/sj.onc.1210440; published online 2 April 2007 [ABSTRACT FROM AUTHOR]

von Hippel–Lindau (VHL) disease is a dominantly inherited family cancer syndrome characterized by the development of retinal and central nervous system haemangioblastomas, renal cell carcinoma (RCC) and phaeochromocytoma. Specific germline VHL mutations may predispose to haemangioblastomas, RCC and phaeochromocytoma to a varying extent. Although dysregulation of the hypoxia-inducible transcription factor-2 and JunB have been linked to the development of RCC and phaeochromocytoma, respectively, the precise basis for genotype–phenotype correlations in VHL disease have not been defined. To gain insights into the pathogenesis of RCC in VHL disease we compared gene expression microarray profiles in a RCC cell line expressing a Type 1 or Type 2B mutant pVHL (RCC-associated) to those of a Type 2A or 2C mutant (not associated with RCC). We identified 19 differentially expressed novel VHL target genes linked to RCC development. Eight targets were studied in detail by quantitative real-time polymerase chain reaction (three downregulated and five upregulated by wild-type VHL) and for six genes the effect of VHL inactivation was mimicked by hypoxia (but hypoxic-induction of smooth muscle alpha-actin 2 was specific for a RCC cell line). The potential role of four RCC-associated VHL target genes was assessed in vitro. NB thymosin beta (TMSNB) and proteinase-activated receptor 2 (PAR2) (both downregulated by wt pVHL) increased cell growth and motility in a RCC cell line, but aldehyde dehydrogenase (ALDH)1 and ALDH7 had no effect. These findings implicate TMSNB and PAR2 candidate oncogenes in the pathogenesis of VHL-associated RCC.Oncogene (2007) 26, 1661–1672. doi:10.1038/sj.onc.1209932; published online 25 September 2006 [ABSTRACT FROM AUTHOR]

A highly efficient and versatile synthetic approach to the synthesis of pyrido[4', 3': 4]thieno[2,3-d]pyrimidines (4, 14, 15, 21) and their heterofused (e.g., triazolo-, triazino-, imidazo-, and tetrazolo-,) pyridothienopyrimidines (5–9, 16, 17, 22–24) is described utilizing 2-amino-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester ( 2 ) and diethyl 2-isothio-cyanate-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3,6-dicarboxylate ( 10 ) as starting materials. [ABSTRACT FROM AUTHOR]

Epigenetic alterations in the 11p15.5 imprinted gene cluster are frequent in human cancers and are associated with disordered imprinting of insulin-like growth factor (IGF)2 and H19. Recently, an imprinted gene cluster at 14q32 has been defined and includes two closely linked but reciprocally imprinted genes, DLK1 and GTL2, that have similarities to IGF2 and H19, respectively. Both GTL2 and H19 are maternally expressed RNAs with no protein product and display paternal allele promoter region methylation, and DLK1 and IGF2 are both paternally expressed. To determine whether methylation alterations within the 14q32 imprinted domain occur in human tumorigenesis, we investigated the status of the GTL2 promoter differentially methylated region (DMR) in 20 neuroblastoma tumours, 20 phaeochromocytomas and, 40 Wilms'tumours. Hypermethylation of the GTL2 promoter DMR was detected in 25%of neuroblastomas, 10%of phaeochromocytoma and 2.5%of Wilms'tumours. Tumours with GTL2 promoter DMR hypermethylation also demonstrated hypermethylation at an upstream intergenic DMR thought to represent a germline imprinting control element. Analysis of neuroblastoma cell lines revealed that GTL2 DMR hypermethylation was associated with transcriptional repression of GTL2. These epigenetic findings are similar to those reported in Wilms'tumours in which H19 repression and DMR hypermethylation is associated with loss of imprinting (LOI, biallelic expression) of IGF2. However, a neuroblastoma cell line with hypermethylation of the GTL2 promoter and intergenic DMR did not show LOI of DLK1 and although treatment with a demethylating agent restored GTL2 expression and reduced DLK1 expression. As described for IGF2/H19, epigenetic changes at DLK1/GTL2 occur in human cancers. However, these changes are not associated with DLK1 LOI highlighting differences in the imprinting control mechanisms operating in the IGF2-H19 and DLK1-GTL2 domains. GTL2 promoter and intergenic DMR hypermethylation is associated with the loss of GTL2 expression and this may contribute to tumorigenesis in a subset of human cancers.British Journal of Cancer (2005) 92, 1574-1580. doi:10.1038/sj.bjc.6602478 www.bjcancer.com Published online 29 March 2005 [ABSTRACT FROM AUTHOR]

The terephthalic acid hydrazide (1) reacted with phenyl / benzyl isothiocyanate 2a,b to yield the corresponding bis-thiosemicarbazides 4a,b, via acid hydrolysis of the intermediate 3 whereas cyclization of 4 gave the bis-1,2,4-triazoles 5,6 and bis-1,3,4-thiadiazoles 7,8. Similarly, compound 1 reacted with phenyl isocyannate 9 to give the bis-semicarbazide 10, which was cyclized to the bis-oxadiazole 11 and/or bis-1,2,4-triazole 12 in POCl3 and NaOH respectively. [ABSTRACT FROM AUTHOR]

Orthoaminoester 1 was investigated by the reaction with ethylchloroformate, 5-phenyl-oxadiazol-2-thione and triethylorthoformate to afford the open structures, 2, 13 and 15. These compounds were subjected to ensuing cyclization in one step or more yielding 3-substituted-5-6-dihydro-8H-4- oxopyrido[4′,3′,4,5]thieno[2,3-d]pyrimidine-7(6H)-carboxylic acid ethyl ester derivatives. [ABSTRACT FROM AUTHOR]

In Drosophila, the Slit gene product, a secreted glycoprotein, acts as a midline repellent to guide axonal development during embryogenesis. Three human Slit gene orthologues have been characterised and recently we reported frequent promoter region hypermethylation and transcriptional silencing of SLIT2 in lung, breast, colorectal and glioma cell lines and primary tumours. Furthermore, re-expression of SLIT2 inhibited the growth of cancer cell lines so that SLIT2 appears to function as a novel tumour suppressor gene (TSG). We analysed the expression of SLIT3 (5q35-34) and SLIT1 (1q23.3-q24) genes in 20 normal human tissues. Similar to SLIT2 expression profile, SLIT3 is expressed strongly in many tissues, while SLIT1 expression is neuronal specific. We analysed the 5'CpG island of SLIT3 and SLIT1 genes in tumour cell lines and primary tumours for hypermethylation. SLIT3 was found to be methylated in 12 out of 29 (41%) of breast, one out of 15 (6.7%) lung, two out of six (33%) colorectal and in two out of (29%) glioma tumour cell lines. In tumour cell lines, silenced SLIT3 associated with hypermethylation and was re-expressed after treatment with 5-aza-2'-deoxycytidine. In primary tumours, SLIT3 was methylated in 16%of primary breast tumours, 35%of gliomas and 38%of colorectal tumours. Direct sequencing of bisulphite-modified DNA from methylated tumour cell lines and primary tumours demonstrated that majority of the CpG sites analysed were heavily methylated. Thus, both SLIT2 and SLIT3 are frequently methylated in gliomas and colorectal cancers, but the frequency of SLIT3 methylation in lung and breast cancer is significantly less than that for SLIT2. We also demonstrated SLIT1 promoter region hypermethylation in glioma tumour lines (five out of six; 83%), the methylation frequency in glioma tumours was much lower (two out of 20; 10%). Hence, evidence is accumulating for the involvement of members of the guidance cues molecules and their receptors in tumour development.British Journal of Cancer (2004) 91, 2071-2078. doi:10.1038/sj.bjc.6602222 www.bjcancer.com Published online 9 November 2004 [ABSTRACT FROM AUTHOR]