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61.
Carén H Ejeskär K Fransson S Hesson L Latif F Sjöberg RM Krona C Martinsson T 《Molecular cancer》2005,4(1):10
Background
A common feature of neuroblastoma tumours are partial deletions of the short arm of chromosome 1 (1p-deletions). This is indicative of a neuroblastoma tumour suppressor gene being located in the region. Several groups including our have been studying candidate neuroblastoma genes in the region, but no gene/genes have yet been found that fulfil the criteria for being a neuroblastoma tumour suppressor. Since frequent mutations have not been detected, we have now analyzed the expression and promoter CpG island methylation status of the genes UBE4B, KIF1B, PGD, APITD1, DFFA and PEX14 in the 1p36.22 region in order to find an explanation for a possible down-regulation of this region. 相似文献62.
Kehinde EO Anim JT Mojiminiyi OA Al-Awadi F Shihab-Eldeen A Omu AE Fatinikun T Prasad A Abraham M 《BJU international》2005,96(1):175-180
OBJECTIVE: To assess the effect of five antioxidants on exocrine function of rabbit testes retained in situ for 24 h and 3 months after experimental torsion. MATERIALS AND METHODS: The left testes of peripubertal rabbits were clamped for 60 min, after which the clamps were removed and the testes allowed to reperfuse. The right testes served as internal controls. There were eight rabbits in each of the following experimental groups: (a) sham; (b) 60-min ischaemia followed by reperfusion; (c) 60-min ischaemia followed by left orchidectomy. In five further groups, rabbits were exposed to 60-min ischaemia followed by reperfusion, but received one of the following antioxidants before reperfusion: acetyl salicylic acid, ascorbic acid, allopurinol, quercetin or superoxide dismutase. Both testes were excised at 24 h or 3 months. The degree of lipid peroxidation, a measure of free radical damage, was assessed in testicular tissue homogenates by measuring the tissue levels of malondialdehyde (MDA). The Johnsen score was used to assess the morphological damage at 24 h and 3 months for each group. RESULTS: At 3 months twisted viable testes allowed to reperfuse had higher MDA levels than controls; the left testes of rabbits treated with allopurinol had significantly lower MDA levels than untreated rabbits and rabbits given other antioxidants. Rabbits given quercetin, ascorbic acid or superoxide dismutase had lower (but not significantly) left testicular MDA levels than untreated rabbits, while rabbits given acetyl salicylic acid had even higher levels. Allopurinol-treated rabbits had a Johnsen score of > 7.6 and those given other antioxidants had scores of < 7.6 at 3 months. CONCLUSION: The twisted viable testis treated by orchidopexy contains high free radical levels at 3 months. Of the antioxidants studied, only allopurinol had a beneficial long-term effect, by significantly reducing testicular MDA levels at 3 months. 相似文献
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Impaired wound healing and skin aging are characterized by neutral protease-mediated destruction of matrix macromolecules associated with disturbance in tissue repair. We synthesized a fatty acyl-peptide derivative at aims to simultaneously activate latent TGF-beta through its peptide domain, KFK, and inhibit MMPs through its lipophilic moiety, elaidic acid. Elaidyl-KFK as well as KFK were shown to activate LAP-TGF-beta both in vitro, using a solid phase assay with immobilized LAP-TGF-beta, and ex vivo using human dermal fibroblasts cultures. In both assays, as much as up to 10% of LAP-TGF-beta added could be recovered as active form. KQK, KQFK as well as their lipopeptide counterparts were inactive. Elaidyl-KFK-mediated LAP-TGF-beta activation led to up-regulation of collagen and TIMP-1 production and down regulation of PMA-induced MMP-1 expression in fibroblasts cultures. Those effects could be suppressed by supplementing cell culture medium with blocking TGF-beta antibody. Elaidyl-KFK inhibited MMP-2, MMP-9, MMP-3, MMP-1, in vitro with IC(50) equal to 1.2, 1.0, 0.24 and 8.9 microM, respectively. Its ex vivo inhibitory capacity, as assessed using skin tissue sections, towards the elastin-degrading capacity of MMP-9 was even more pronounced. At a 1 microM concentration, the lipopeptide decreased by up to 80% enzyme activity. Thus, "Lipospondin," i.e. elaidyl-KFK might be considered as a promising model compound to prevent age-associated dermal alterations. 相似文献
66.
RASSF1A interacts with microtubule-associated proteins and modulates microtubule dynamics 总被引:11,自引:0,他引:11
Dallol A Agathanggelou A Fenton SL Ahmed-Choudhury J Hesson L Vos MD Clark GJ Downward J Maher ER Latif F 《Cancer research》2004,64(12):4112-4116
The candidate tumor suppressor gene RASSF1A is inactivated in many types of adult and childhood cancers. However, the mechanisms by which RASSF1A exerts its tumor suppressive functions have yet to be elucidated. To this end, we performed a yeast two-hybrid screen to identify novel RASSF1A-interacting proteins in a human brain cDNA library. Seventy percent of interacting clones had homology to microtubule-associated proteins, including MAP1B and VCY2IP1/C19ORF5. RASSF1A association with MAP1B and VCY2IP1/C19ORF5 was subsequently confirmed in mammalian cell lines. This suggested that RASSF1A may exert its tumor-suppressive functions through interaction with the microtubules. We demonstrate that RASSF1A associates with the microtubules, causing them to exist as hyperstabilized circular bundles. We found that two naturally occurring tumor-associated missense substitutions in the RASSF1A coding region, C65R and R257Q, perturb the association of RASSF1A with the microtubules. The C65R and R257Q in addition to VCY2IP1/C19ORF5 showed reduced ability to induce microtubule acetylation and were unable to protect the microtubules against the depolymerizing action of nocodazole. In addition, wild-type RASSF1A but not the C65R or the R257Q is able to block DNA synthesis. Our data identify a role for RASSF1A in the regulation of microtubules and cell cycle dynamics that could be part of the mechanism(s) by which RASSF1A exerts its growth inhibition on cancer cells. 相似文献
67.
Yotsu-Yamashita M Yasumoto T Yamada S Bajarias FF Formeloza MA Romero ML Fukuyo Y 《Chemical research in toxicology》2004,17(9):1265-1271
Outbreaks of seaweed poisonings are widely spread over the pacific area. Fatal glycosidic macrolides, polycavernosides, and potent tumor promoters, aplysiatoxins, have been previously isolated from edible seaweed. During 2002-2003, three fatal poisoning incidents occurred resulting from ingestion of two edible red alga, Acanthophora specifera and Gracilaria edulis, in Philippines causing eight deaths among 36 patients. Analytical methods for polycavernosides and aplysiatoxins were first developed, and the causative toxin from G. edulis, collected during the second poisoning event on December 2, 2002, was then investigated. The semipurified toxic fraction obtained from this alga based on mouse bioassay was applied to LC-diode array detection (LC-DAD) and LC/electrospray-MS (LC/ESI-MS) analyses. Both LC-DAD and LC/MS chromatograms of this fraction suggested the presence of polycavernoside A (PA) by comparison with the authentic PA. The amount of PA in the alga was estimated as 84 and 72 nmol/kg, using the standard calibration curves for LC-DAD and for LC/ESI-MS in single ion monitoring (SIM) mode, respectively. Other polycavernoside congeners, A2, A3, and B2, and aplysiatoxin and debromoaplysiatoxin were less than the detection limit (2 nmol/kg alga, signal-to-noise ratio: 3) by LC/ESI-MS SIM analysis. In ESI-MS/MS, authentic polycavernosides showed the daughter ions corresponding to a sequential loss of fucosylxylose residues. These fragmentations were applied to LC/ESI-MS/MS for polycavernosides in selective reaction monitoring (SRM) mode. On SRM mass chromatograms, the toxic fraction from the alga showed the peaks corresponding to PA, supporting the identification of PA as the cause of poisoning of G. edulis in Philippines. 相似文献
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Agathanggelou A Bièche I Ahmed-Choudhury J Nicke B Dammann R Baksh S Gao B Minna JD Downward J Maher ER Latif F 《Cancer research》2003,63(17):5344-5351
70.
Morris MR Hesson LB Wagner KJ Morgan NV Astuti D Lees RD Cooper WN Lee J Gentle D Macdonald F Kishida T Grundy R Yao M Latif F Maher ER 《Oncogene》2003,22(43):6794-6801
To investigate the role of epigenetic gene silencing in the pathogenesis of Wilms' tumour and renal cell carcinoma (RCC), we determined their methylation profile using a candidate gene approach. Thus, 40 Wilms' tumours and up to 49 adult RCC were analysed by methylation-specific PCR for promoter methylation at CASP8, CDH1, CDH13, DAPK, MGMT, NORE1A, p14ARF and RARB2 in primary Wilms' tumours and CASP8, CDH1, CDH13, CRBP1, DAPK, MGMT, MT1G, NORE1A, p16INK4a, SDHB and RARB2 in primary RCC. Both tumour sample sets had previously been analysed for RASSF1A promoter methylation, and p16INK4a methylation results were also available for the Wilms' tumour samples. Wilms' tumours demonstrated a high incidence of methylation at CASP8 (43%) and MGMT (30%), intermediate frequencies at NORE1A (15%), p14ARF (15%), p16INK4a (10%), DAPK (11%) and CRBP1 (9%), but promoter methylation was rare or absent at RARB2 (0%), CDH13 (0%) and CDH1 (3%). No association was detected between methylation of RASSF1A, CASP8 or MGMT in individual tumours. The frequency of MGMT methylation was higher in stage 1 and 2 tumours (50%) than in stage 3 and 4 tumours (17%) but this did not reach statistical significance (P=0.06). RCC were most frequently methylated at DAPK (24%), MT1G (20%), NORE1A (19%), CDH1 (16%) and MGMT (9%) and not or rarely at SDHB (4%), RARB2 (0%), p16INK4a (0%) and CDH13 (3%). There were no associations between methylation of RASSF1A, DAPK and CDH1 in individual tumours. Papillary RCC demonstrated a higher frequency of DAPK methylation (43%) than clear cell tumours (19%) (P=0.14). We have demonstrated that de novo promoter methylation is frequent in Wilms' tumour and RCC, and these data enable methylation profiles to be constructed for each tumour type. Thus, combining our results with data published previously, it appears that promoter methylation occurs frequently (> or =20% of primary tumours) at CASP8, SLIT2 and RASSF1A in Wilms' tumour and at RASSF1A, TIMP3, DAPK, SLIT2, MT1G and GSTP1 in RCC. 相似文献