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61.
Aldo Becciolini Manuela Balzi Paola Faraoni Elena Tisti Giorgia Zappoli Thyrion Valentino Giach Luca Bandettini Christopher S. Potten 《Acta oncologica (Stockholm, Sweden)》1998,37(1):65-71
Cell kinetics parameters have been analysed in colonic mucosa at different distances from a tumour in patients with colon carcinoma. Total cell number (TCN), H thymidine labelling index (TLI), mitotic index (MI), Goblet cell index (GCI) and the distribution of labelled cells along the crypt column (cell position frequency plot) were determined in well-aligned crypts. Total cell number, GCI and the labelled cell position frequency plots were similar in different samples from the same individual. A negative linear correlation between TCN and TLI was observed. The analysis of the cell position plots showed two patterns 1) with a high concentration in the bottom fifth of the crypt and 2) with frequent labelled cells at high positions. Whereas a negative correlation between overall TLI and the percent contribution to the TLI of the lowermost fifth was seen, the correlation was positive for the next 3 fifths and labelling was absent in the last part of the crypt. 相似文献
62.
Kirsti A Bocskay Deliang Tang Manuela A Orjuela Xinhua Liu Dorothy P Warburton Frederica P Perera 《Cancer epidemiology, biomarkers & prevention》2005,14(2):506-511
Molecular and traditional epidemiology studies have indicated a possible relationship between in utero environmental exposures and increased risk for childhood cancers, especially acute leukemias. Chromosomal aberrations have been associated with environmental exposures and cancer risk in adults. In order to more clearly define the association between prenatal exposures to carcinogenic polycyclic aromatic hydrocarbons (PAH) and chromosomal aberrations, chromosomal aberration frequencies were measured in a subset of 60 newborns from the Columbia Center for Children's Environmental Health (CCCEH) Prospective Cohort Study. The subset was composed of African American and Dominican, nonsmoking mother-newborn pairs residing in low-income neighborhoods of New York City, who were exposed to varying levels of airborne PAHs. Prenatal exposure was assessed by questionnaire, personal air monitoring during the third trimester, and PAH-DNA adducts in umbilical cord blood. Chromosomal aberrations were measured in cord blood lymphocytes by fluorescence in situ hybridization. PAH-DNA adducts were not associated with chromosomal aberrations. However, airborne PAHs were significantly associated with stable aberration frequencies in cord blood (P < 0.01). Moreover, stable aberration frequencies were significantly higher among African American newborns compared with Dominican, despite no significant differences in PAH exposure. These results show for the first time an association between prenatal exposure to airborne carcinogenic PAHs and chromosomal aberrations in cord blood, suggesting that such prenatal exposures have the potential to cause cytogenetic damage that has been related to increased cancer risk in other populations. If confirmed, this finding may open new avenues for prevention. 相似文献
63.
DNA methylation changes measured in pre‐diagnostic peripheral blood samples are associated with smoking and lung cancer risk
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Allison Hodge Manuela Bianca Assumma Chol‐Hee Jung Jessica Chung Francesca Fasanelli Florence Guida Gianluca Campanella Marc Chadeau‐Hyam Kjell Grankvist Mikael Johansson Ugo Ala Paolo Provero Ee Ming Wong Jihoon Joo Dallas R. English Nabila Kazmi Eiliv Lund Christian Faltus Rudolf Kaaks Angela Risch Myrto Barrdahl Torkjel M. Sandanger Melissa C. Southey Graham G. Giles Mattias Johansson Paolo Vineis Gianluca Severi 《International journal of cancer. Journal international du cancer》2017,140(1):50-61
DNA methylation changes are associated with cigarette smoking. We used the Illumina Infinium HumanMethylation450 array to determine whether methylation in DNA from pre‐diagnostic, peripheral blood samples is associated with lung cancer risk. We used a case‐control study nested within the EPIC‐Italy cohort and a study within the MCCS cohort as discovery sets (a total of 552 case‐control pairs). We validated the top signals in 429 case‐control pairs from another 3 studies. We identified six CpGs for which hypomethylation was associated with lung cancer risk: cg05575921 in the AHRR gene (p‐valuepooled = 4 × 10?17), cg03636183 in the F2RL3 gene (p‐valuepooled = 2 × 10 ? 13), cg21566642 and cg05951221 in 2q37.1 (p‐valuepooled = 7 × 10?16 and 1 × 10?11 respectively), cg06126421 in 6p21.33 (p‐valuepooled = 2 × 10?15) and cg23387569 in 12q14.1 (p‐valuepooled = 5 × 10?7). For cg05951221 and cg23387569 the strength of association was virtually identical in never and current smokers. For all these CpGs except for cg23387569, the methylation levels were different across smoking categories in controls (p‐valuesheterogeneity ≤ 1.8 x10 ? 7), were lowest for current smokers and increased with time since quitting for former smokers. We observed a gain in discrimination between cases and controls measured by the area under the ROC curve of at least 8% (p‐values ≥ 0.003) in former smokers by adding methylation at the 6 CpGs into risk prediction models including smoking status and number of pack‐years. Our findings provide convincing evidence that smoking and possibly other factors lead to DNA methylation changes measurable in peripheral blood that may improve prediction of lung cancer risk. 相似文献
64.
A fluorescent curcumin-based Zn(II)-complex reactivates mutant (R175H and R273H) p53 in cancer cells
Alessia Garufi Daniela Trisciuoglio Manuela Porru Carlo Leonetti Antonella Stoppacciaro Valerio D’Orazi Maria Laura Avantaggiati Alessandra Crispini Daniela Pucci Gabriella D’Orazi 《Journal of experimental & clinical cancer research : CR》2013,32(1):72
Background
Mutations of the p53 oncosuppressor gene are amongst the most frequent aberration seen in human cancer. Some mutant (mt) p53 proteins are prone to loss of Zn(II) ion that is bound to the wild-type (wt) core, promoting protein aggregation and therefore unfolding. Misfolded p53 protein conformation impairs wtp53-DNA binding and transactivation activities, favouring tumor growth and resistance to antitumor therapies. Screening studies, devoted to identify small molecules that reactivate mtp53, represent therefore an attractive anti-cancer therapeutic strategy. Here we tested a novel fluorescent curcumin-based Zn(II)-complex (Zn-curc) to evaluate its effect on mtp53 reactivation in cancer cells.Methods
P53 protein conformation was examined after Zn-curc treatment by immunoprecipitation and immunofluorescence assays, using conformation-specific antibodies. The mtp53 reactivation was evaluated by chromatin-immunoprecipitation (ChIP) and semi-quantitative RT-PCR analyses of wild-type p53 target genes. The intratumoral Zn-curc localization was evaluated by immunofluorescence analysis of glioblastoma tissues of an ortothopic mice model.Results
The Zn-curc complex induced conformational change in p53-R175H and -R273H mutant proteins, two of the most common p53 mutations. Zn-curc treatment restored wtp53-DNA binding and transactivation functions and induced apoptotic cell death. In vivo studies showed that the Zn-curc complex reached glioblastoma tissues of an ortothopic mice model, highlighting its ability to crossed the blood-tumor barrier.Conclusions
Our results demonstrate that Zn-curc complex may reactivate specific mtp53 proteins and that may cross the blood-tumor barrier, becoming a promising compound for the development of drugs to halt tumor growth. 相似文献65.
Nehal Elkhoshkhany Samir Marzouk Mohammed El-Sherbiny Heba Ibrahim Bozena Burtan-Gwizdala Mohammed S. Alqahtani Khalid I. Hussien Manuela Reben El Sayed Yousef 《Materials》2022,15(15)
A novel series of glass, consisting of B2O3, Bi2O3, TeO2, and TiO2 (BBTT) containing rare earth oxide RE2O3, where RE is La, Ce, Sm, Er, and Yb, was prepared. We investigated the structural, optical, and gamma attenuation properties of the resultant glass. The optical energy bands, the linear refractive indices, the molar refractions, the metallization criteria, and the optical basicity were all determined for the prepared glass. Furthermore, physical parameters such as the density, the molar volume, the oxygen molar volume, and the oxygen packing density of the prepared glass, were computed. Both the values of density and optical energy of the prepared glass increased in the order of La2O3, Ce2O3, Sm2O3, Er2O3, and then Yb2O3. In addition, the glass doped with Yb2O3 had the lowest refractive index, electronic polarizability, and optical basicity values compared with the other prepared glass. The structures of the prepared glass were investigated by the deconvolution of infrared spectroscopy, which determined that TeO4, TeO3, BO4, BO3, BiO6, and TiO4 units had formed. Furthermore, the structural changes in glass are related to the ratio of the intensity of TeO4/TeO3, depending on the type of rare earth. It is also clarified that the resultant glass samples are good attenuators against low-energy radiation, especially those that modified by Yb2O3, which exhibited superior shielding efficiency at energies of 622, 1170, and 1330 keV. The optical and gamma ray spectroscopy results of the prepared glass show that it is a good candidate for nonlinear optical fibers, laser solid material, and optical shielding protection. 相似文献
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68.
Stefan Pleus Andreas Stuhr Manuela Link Cornelia Haug Guido Freckmann 《Journal of diabetes science and technology》2022,16(3):649
Background:There is an increasing use of continuous glucose monitoring (CGM) by people with diabetes. Measurement performance is often characterized by the mean absolute relative difference (MARD). However, MARD is influenced by a number of factors and little is known about whether MARD is stable throughout the day.Material and Methods:A total of 24 participants with type 1 diabetes were enrolled in the study. The study was performed for seven in-patient days. Participants wore two CGM systems in parallel and performed additional frequent blood glucose (BG) measurements. On two days, glucose excursions were induced.MARD was calculated between pairs of CGM and BG values, with BG values serving as reference values. ARD values calculated from CGM-BG pairs were grouped by hour of the day. Results were analyzed separately for glucose excursion days and for regular days.Results:Total MARDs for the complete study duration were 12.5% ± 3.6% and 13.2% ± 2.4% (n = 24). Throughout the day marked variability of MARD was observed (8.0% ± 1.3%-16.3% ± 2.9% (G5); 9.1% ± 1.4%-16.3% ± 5.3% (FL), up to n = 157 each). Low(est) MARD values were observed before breakfast and dinner, when subjects were in or near a fasting state. Especially after breakfast and lunch, MARD values were higher than average.Conclusions:Analytical performance of the two CGM systems, assessed by MARD, was found to vary markedly throughout the day. Activities of daily life likely triggered these variations. An increasing number of CGM users base therapeutic decisions on CGM values, and they should be aware of these variations of performance throughout the day. 相似文献
69.
Sylvia J. Gasparini Karen Tessmer Miriam Reh Stephanie Wieneke Madalena Carido Manuela Vlkner Oliver Borsch Anka Swiersy Marta Zuzic Olivier Goureau Thomas Kurth Volker Busskamp Günther Zeck Mike O. Karl Marius Ader 《The Journal of clinical investigation》2022,132(12)
Once human photoreceptors die, they do not regenerate, thus, photoreceptor transplantation has emerged as a potential treatment approach for blinding diseases. Improvements in transplant organization, donor cell maturation, and synaptic connectivity to the host will be critical in advancing this technology for use in clinical practice. Unlike the unstructured grafts of prior cell-suspension transplantations into end-stage degeneration models, we describe the extensive incorporation of induced pluripotent stem cell (iPSC) retinal organoid–derived human photoreceptors into mice with cone dysfunction. This incorporative phenotype was validated in both cone-only as well as pan-photoreceptor transplantations. Rather than forming a glial barrier, Müller cells extended throughout the graft, even forming a series of adherens junctions between mouse and human cells, reminiscent of an outer limiting membrane. Donor-host interaction appeared to promote polarization as well as the development of morphological features critical for light detection, namely the formation of inner and well-stacked outer segments oriented toward the retinal pigment epithelium. Putative synapse formation and graft function were evident at both structural and electrophysiological levels. Overall, these results show that human photoreceptors interacted readily with a partially degenerated retina. Moreover, incorporation into the host retina appeared to be beneficial to graft maturation, polarization, and function. 相似文献
70.