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  • 1
    Keywords: CELLS ; EXPRESSION ; carcinoma ; PROTEINS ; mechanisms ; BREAST-CANCER ; PROGRESSION ; statistics ; oligonucleotides ; INTEGRIN ; heredity ; MANAGEMENT ; TUMOR-METASTASIS ; CD44 ; antisense-oligonucleotide ; CC531 colorectal cancer cells ; extracellular matrix protein:osteopontin ; liver metastasis of colorectal cancer ; modulation of expression
    Abstract: Development of hepatic metastasis is responsible for most of colorectal cancer-related deaths. Osteopontin (OPN) is a small integrin-binding N-linked glycoprotein, which plays a crucial role in the formation of hepatic metastasis. This study aimed to suppress Opn expression by an antisense-oligonucleotide (ASO(Opn)) to decrease liver metastasis in vivo. The effect of ASO(Opn) was investigated in vitro in CC531(lacZ) colorectal cancer cells in comparison to sense (SO) or nonsense (NSO) oligomers, by determining mRNA and protein expression levels, as well as cell survival. For in vivo treatment, CC531(lacZ) cells were intraportally inoculated into rats to compare the effects of ASO, SO and NSO oligomers, following prolonged subcutaneous administration by osmotic mini-pumps. The resulting CC531(lacZ) tumor cell load in the liver was measured by a beta-galactosidase assay. Proliferation of CC531(lacZ) cells in vitro was significantly decreased after ASO(Opn) and SO treatment (P〈0.001). Liver metastasis development was reduced as long as ASO(Opn) was administered, but this effect was rapidly blunted following the end of the ASO(Opn) administration. In contrast, administration of the SO resulted in a tumor load reduction, which surprisingly surpassed the ASO(Opn) effect in vivo in terms of a long-lasting metastasis suppression, which was accompanied with increased survival of the animals. Administration of the ASO(Opn) in rats was effective in decreasing their liver metastasis. The short-lived effect might be extended by modifications suited to increase the ASOs' half-life. In addition, there was a superior anti-metastatic effect caused by the SO, which has not been reported previously.
    Type of Publication: Journal article published
    PubMed ID: 21852811
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  • 2
    Abstract: The colonic opportunist Streptococcus gallolyticus subspecies gallolyticus (SGG) is potentially associated with colorectal cancer (CRC). Large-scale seroepidemiological data for SGG antibodies and their possible association with CRC is currently missing. Associations between CRC and antibody responses to SGG were examined in 576 CRC cases and 576 controls matched by sex, age and province from a population-based multicase-control project (MCC-Spain). MCC-Spain was conducted between 2008 and 2013 in 12 Spanish provinces. Antibody responses to recombinant affinity-purified SGG pilus proteins Gallo1569, 2039, 2178 and 2179 were analysed by multiplex serology. Polyomavirus (PyV) JC VP1 and PyV 6 VP1 proteins served as disease-specificity controls. In the control population, antibody responses to pilus proteins were mostly weak. Antibody responses to individual pilus proteins Gallo2039 (OR: 1.58, 95% CI: 1.09-2.28), Gallo2178 (OR: 1.58, 95% CI: 1.09-2.30) and Gallo2179 (OR: 1.45, 95% CI: 1.00-2.11) were significantly associated with CRC risk. The association was stronger for positivity to two or more pilus proteins of Gallo1569, Gallo2178 and Gallo2179 (OR:1.93, 95% CI: 1.04-3.56) and for double-positivity to Gallo2178 and Gallo2179 (OR: 3.54, 95% CI: 1.49-8.44). The association between SGG infection and CRC risk was stronger among individuals younger than 65 years. For the first time we demonstrated a statistically significant association of exposure to SGG antigens and CRC in a large seroepidemiological study. These results should stimulate further studies on the role of SGG in CRC pathogenesis.
    Type of Publication: Journal article published
    PubMed ID: 26537841
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  • 3
    Keywords: CANCER ; CANCER CELLS ; CELLS ; EXPRESSION ; GROWTH ; IN-VITRO ; tumor ; TUMOR-CELLS ; AGENTS ; CELL ; Germany ; IN-VIVO ; KINASE ; MODEL ; VITRO ; VIVO ; DISEASE ; liver ; DRUG ; EFFICIENCY ; TIME ; PATIENT ; RAT ; RATS ; MR ; TARGET ; RAT-LIVER ; ASSAY ; resistance ; METASTASIS ; colorectal cancer ; COLORECTAL-CANCER ; metastases ; chemotherapy ; COLORECTAL LIVER METASTASES ; CANCER-CELLS ; doxorubicin ; STRATEGIES ; NETHERLANDS ; SAFETY ; LIVER METASTASES ; sensitivity ; ARTERY ; AGENT ; ORDER ; ONCOLOGY ; GEMCITABINE ; RE ; WEIGHT ; PHASE ; ERK ; technique ; irinotecan ; COLON-CARCINOMA CELLS ; PROSPECTIVE RANDOMIZED TRIAL ; systemic ; PROFILE ; chemoembolisation ; drug eluting beads ; FLOXURIDINE
    Abstract: Systemic chemotherapy has limited success in treating liver metastasis of colorectal cancer. Alternative approaches such as hepatic arterial infusion or trans arterial chemoembolisation aim to deliver the chemotherapy locally to address the predominant liver disease. Chemoembolisation with drug eluting beads (DEB) designed to deliver drug at the target over a protracted period of time is a new strategy to reduce the tumor burden of liver metastases. To test this hypothesis, DEB possessing anionic groups capable of ionically complexing with cationic drugs were synthesised by a suspension polymerisation method and were fractionated to produce an average size of 75 mu m. The DEB were loaded with the desired concentration of either doxorubicin hydrochloride or irinotecan hydrochloride prior to administration by immersion in the drug solution, yielding essentially 100% loading efficiency. To determine their effect in vivo, a transplantable orthotopic and isogenic rat liver metastasis model was used which is based on intraportal injection of 4 x 10(6) beta-galactosidase transfected CC531 rat colorectal cancer cells into male WAG/Rij rats. By MTT assay, the cells were shown to be sensitive to both drugs in vitro with the IC50 being by two orders of magnitude lower for doxorubicin (110 nM after 72 h) compared to irinotecan (25 mu M after 72 h). For the in vivo phase, a differential expression of the ERK MAP kinase between tumor cells cultured in vitro and those inoculated in vivo was noted using Western blotting techniques. This was considered to be indicative of passage-induced cell senescence that reduced the sensitivity of the tumor cells to DEB chemoembolisation. This notwithstanding, administration of DEB loaded with irinotecan or doxorubicin by single injection into the hepatic artery showed significant anticancer activity, as measured by a reduction in the tumor burden of the liver and a corresponding reduction in liver weight. Comparing the two agents, irinotecan appears more advantageous because of its significant activity and excellent tolerability following administration at two dosages of either 20 or 30 mg/kg. Doxorubicin showed a narrower window of activity, being effective at 4 mg/kg but ineffective at the lower dose of 2 mg/kg. We conclude that chemoembolisation with DEB with either agent may have potential for treating patients with colorectal liver metastasis, although irinotecan DEB appeared to have a more favourable safety profile
    Type of Publication: Journal article published
    PubMed ID: 18259882
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  • 4
  • 5
    ISSN: 1432-0738
    Keywords: Mutagenicity ; Metabolic activation ; Lung ; Liver ; Airborne particulate matter ; P-450
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In this study liver and lung homogenates of untreated and Aroclor 1254-pretreated rats (Wistar) and mice (Swiss) were compared for their P-450 content and their capacity to activate extracts of airborne particulate matter, sampled indoors and outdoors. Results show that in addition to liver, lung homogenates of rat (Wistar) and mouse (Swiss) are also able to activate extracts of airborne particulate matter in a comparative way. Uninduced liver and lung homogenates showed only minor differences in activation capacity in the metabolism of airborne particles. In contrast to liver homogenates, Aroclor 1254 pretreatment of test animals did not give strong induction of metabolic activation capacity of lung homogenates. P-450 content was observed in all liver and lung homogenates of mouse and rat and in human lung homogenates. The results obtained in this study suggest that the respiratory tract may be an important site for in vivo bioactivation of respirable particles.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1246
    Keywords: Indoor pollution ; Carbon monoxide ; Carboxy hemoglobin ; Biological monitoring
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary CO levels in exhaled breath were measured in 29 residents of flats, equipped with a flueless geiser (an instantaneous gas-fired water heater). The flats were selected because they had a geiser with a CO concentration of more than 250 parts per million in its flue gases. Small, but in some cases statistically significant increases in CO levels in exhaled breath were found in both smokers and non smokers, and after periods of cooking and dishwashing when the geisers had been used. Calculated COHb levels remained well below 2.5% for non smokers, but were generally higher for smokers.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1246
    Keywords: Indoor air pollution ; Nitrogen dioxide ; Passive smoking ; Gasfired appliances ; Hydroxyproline excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The urinary hydroxyproline excretion was investigated in a population of 6- to 9-year-old schoolchildren living in the Netherlands. Early morning samples of urine were collected at the end of a week in which personal and home monitoring for nitrogen dioxide (NO2) was carried out, and in which detailed information on gas appliances and on parental smoking habits was gathered. In addition, the pulmonary function of the children was measured, and their respiratory symptoms were collected using a standardized questionnaire which was completed by the parents. The hydroxyproline concentrations were standardized for urinary creatinine content. The hydroxyproline/creatinine ratio (HOP/C ratio) was found to be unrelated to NO2 exposure. The presence of major NO2-sources in the kitchen, vented and unvented gas-fired waterheaters, was significantly associated with elevated HOP/C ratios, due to a negative relationship with the creatinine concentration. There was a tendency for HOP/C to increase with the amount of tobacco smoked in the presence of a child. Respiratory symptoms and pulmonary function were unrelated to HOP/C. In this population, the urinary HOP/C ratio was not found to be a close correlate of exposure to NO2 or tobacco smoke, and of respiratory symptoms and pulmonary function.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 44 (1989), S. 0 
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The association between living in damp homes and the prevalence of health symptoms was investigated in a population of 519 occupants (adults and children) of 185 homes. Positive associations were found between the reporting of respiratory and some other health symptoms and living in a damp home. The concentration of vaiable mould spores in indoor air was measured, using modified Andersen samplers, in the living rooms of a sample of 36 homes. The results were compared with the occurrence of dampness characteristics in their homes as reported by the occupants. Homes with at least two dampness characteristics showed higher average spore counts and higher prevalence of respiratory symptoms.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Munksgaard International Publishers
    Indoor air 2 (1992), S. 0 
    ISSN: 1600-0668
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Architecture, Civil Engineering, Surveying , Medicine
    Notes: During the winter of 1988/1989, the relationships between the prevalence of work-related health and indoor climate complaints and a number of building, management, workplace and personal characteristics have been investigated in a study in more than 60 office buildings located throughout the Netherlands.To collect the information, a questionnaire was prepared on health and indoor climate complaints and personal and workplace characteristics. A checklist was used to obtain information on building characteristics More than 7000 questionnaires were completed by the regular users of the buildings investigated.The results showed that the prevalence of symptoms was higher in air-conditioned buildings than in naturally or mechanically ventilated buildings. some other variables were also related with most work-related complaints after adjustment for selected management, personal, workplace and job characteristics. These included gender, work satisfaction in general, presence of allergies and/or respiratory symptoms, and personal control over temperature at the workplace. No differences were found in symptom prevalences between buildings with spray and steam humidification. The combination of air-conditioning and humidification did not lead to further increases in the prevalence of complaints as compared to buildings with only airconditioning or only humidification.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A number of techniques for the enumeration and identification of viable mould propagules in the indoor air of houses were evaluated in order to document to what extent different results are obtained when different methods are used. A comparison was made between the results obtained with five commercially available air sampling devices (Slit-to agar sampler, N6-Andersen sampler, Surface Air System sampler, Reuter Centrifugal Air sampler. Gelatine Filter sampler) and a non-volumetric sampler (the Open Petri Dish), in combination with four culture media (malt extract agar, dichloran glycerol-18 agar, oxytetracycline glucose yeast extract agar and dichloran rose bengal chloramphenicol agar). The coefficients of variation were high (generally 〈 20%) for all combinations. Statistical analysis showed that the Slit sampler and the N6-Andersen sampler in combination with DG18 and MEA gave the best precision and the highest yield in terms of colony forming units per square cubic meter of air (CFU/m3) and number of species isolated.
    Type of Medium: Electronic Resource
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