scholarly journals Mucins (MUC1 and MUC3) of Gastrointestinal and Breast Epithelia Reveal Different and Heterogeneous Tumor-associated Aberrations in Glycosylation

1997 ◽  
Vol 45 (11) ◽  
pp. 1547-1557 ◽  
Author(s):  
Yi Cao ◽  
Dietmar Blohm ◽  
B. Michael Ghadimi ◽  
Peter Stosiek ◽  
Pei-Xiang Xing ◽  
...  

In a comprehensive study, we examined the expression of the membrane and secretory mucins MUC1 and MUC3, respectively, in normal and neoplastic gastrointestinal and breast epithelia before and after specific alterations of their glycan structures by neuraminidase, α-fucosidase, or carbohydrate-specific periodate oxidation. MUC1 mRNA was also identified in normal colorectal tissues by in situ hybridization. The data revealed that normal colorectal epithelia express both MUC1 mRNA and protein, which were detectable after periodate oxidation with all tested MUC1-specific antibodies. During tumorigenesis in the colon, MUC1 became recognizable without periodate treatment concomitantly with highly dysplastic lesions and the malignant state. In the breast, in which MUC1 is detectable with most antibodies in normal epithelium as well as in carcinomas, staining could be enhanced by pretreatment with periodate and casually by enzyme treatments. MUC3 was detectable in normal and neoplastic colorectal tissues and was more intensely stained after periodate oxidation. It was absent in normal breast even after pretreatment but was expressed in seven of 20 breast carcinomas. Therefore, incomplete glycosylation, abnormal distribution, and ectopic expression of mucins are characteristics of malignancy. Periodate oxidation may be widely applicable to immunohistochemistry for examining changes in glycosylation and for detecting antigens masked by glycans. (J Histochem Cytochem 45:1547–1557, 1997)

2020 ◽  
Vol 01 ◽  
Author(s):  
Henrik Jensen ◽  
Pernille D. Pedersen

Aims: To evaluate the real-life effect of photocatalytic surfaces on the air quality at two test-sites in Denmark. Background: Poor air quality is today one of the largest environmental issues, due to the adverse effects on human health associated with high levels of air pollution, including respiratory issues, cardiovascular disease (CVD), and lung cancer. NOx removal by TiO2 based photocatalysis is a tool to improve air quality locally in areas where people are exposed. Methods: Two test sites were constructed in Roskilde and Copenhage airport. In Roskilde, the existing asphalt at two parking lots was treated with TiO2 containing liquid and an in-situ ISO 22197-1 test setup was developed to enable in-situ evaluation of the activity of the asphalt. In CPH airport, photocatalytic concrete tiles were installed at the "kiss and fly" parking lot, and NOx levels were continuously monitored in 0.5 m by CLD at the active site and a comparable reference site before and after installation for a period of 2 years. Results: The Roskilde showed high stability of the photocatalytic coating with the activity being largely unchanged over a period of 2 years. The CPH airport study showed that the average NOx levels were decreased by 12 % comparing the before and after NOx concentrations at the active and reference site. Conclusion: The joined results of the two Danish demonstration projects illustrate a high stability of the photocatalytic coating as well as a high potential for improvements of the real-life air quality in polluted areas.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Vladimir V. Strelnikov ◽  
Ekaterina B. Kuznetsova ◽  
Alexander S. Tanas ◽  
Viktoria V. Rudenko ◽  
Alexey I. Kalinkin ◽  
...  

AbstractCell transmembrane receptors and extracellular matrix components play a pivotal role in regulating cell activity and providing for the concerted integration of cells in the tissue structures. We have assessed DNA methylation in the promoter regions of eight integrin genes, two nidogen genes, and the dystroglycan gene in normal breast tissues and breast carcinomas (BC). The protein products of these genes interact with the basement membrane proteins LAMA1, LAMA2, and LAMB1; abnormal hypermethylation of the LAMA1, LAMA2, and LAMB1 promoters in BC has been described in our previous publications. In the present study, the frequencies of abnormal promoter hypermethylation in BC were 13% for ITGA1, 31% for ITGA4, 4% for ITGA7, 39% for ITGA9, 38% for NID1, and 41% for NID2. ITGA2, ITGA3, ITGA6, ITGB1, and DAG1 promoters were nonmethylated in normal and BC samples. ITGA4, ITGA9, and NID1 promoter hypermethylation was associated with the HER2 positive tumors, and promoter hypermethylation of ITGA1, ITGA9, NID1 and NID2 was associated with a genome-wide CpG island hypermethylated BC subtype. Given that ITGA4 is not expressed in normal breast, one might suggest that its abnormal promoter hypermethylation in cancer is non-functional and is thus merely a passenger epimutation. Yet, this assumption is not supported by our finding that it is not associated with a hypermethylated BC subtype. ITGA4 acquires expression in a subset of breast carcinomas, and methylation of its promoter may be preventive against expression in some tumors. Strong association of abnormal ITGA4 hypermethylation with the HER2 positive tumors (p = 0.0025) suggests that simultaneous presence of both HER2 and integrin α4 receptors is not beneficial for tumor cells. This may imply HER2 and integrin α4 signaling pathways interactions that are yet to be discovered.


2001 ◽  
Vol 8 (5) ◽  
pp. 415-418 ◽  
Author(s):  
Nils M. Diaz

Background Laboratory testing of HER2/neu in breast carcinoma has become vital to patient care following the approval of trastuzumab as the first therapy to target the HER2/neu oncoprotein. Initial clinical trials used immunohistochemistry (IHC) to test for HER2/neu overexpression in order to select patients for therapy. Fluorescence in situ hybridization (FISH), which tests for gene amplification, is more specific and sensitive than IHC when either assay is compared with HER2/neu overexpression as determined by Northern or Western blot analysis. Many weak overexpressors on IHC testing are not gene amplified on FISH analysis. Such weak overexpressors may be considered false-positives and raise the question of how best to test for HER2/neu. Methods The literature was surveyed regarding testing for HER2/neu overexpression in breast carcinomas and alternative testing strategies. Results False-positive results are a significant problem when IHC is exclusively used to test for HER2/neu overexpression. The false-positives are overwhelmingly confined to the group of 2+ positives and do not respond to targeted therapy. In contrast, concordance between IHC and FISH is high when immunostaining is interpreted as either negative or strongly positive (3+). Whereas some recent studies have suggested that FISH may better predict response to anti-HER2/neu therapy than IHC, others have indicated that IHC is as effective a predictor as FISH. IHC is less technically demanding and costly than FISH. Conclusions IHC analysis of HER2/neu in breast carcinoma is a useful predictor of response to therapy with trastuzumab when strongly positive. Negative immunostaining is highly concordant with a lack of gene amplification by FISH. Most weakly positive overexpressors are false-positives on testing with FISH. Thus, screening of breast carcinomas with IHC and confirmation of weakly positive IHC results by FISH is an effective evolving strategy for testing HER2/neu as a predictor of response to targeted therapy.


2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Dawei Zhang ◽  
Lihong Zhang ◽  
Bingzhe Wang ◽  
Guangzhe Piao

Stable lyotropic chiral nematic liquid crystals (N*-LCs) of cellulose nanocrystals (CNs) were prepared via hydrolysis using sulfuric acid. The lyotropic N*-LCs were used as an asymmetric reaction field to synthesize polyaniline (PANI) onto CNs by in situ polymerization. As a primary step, we examined the mesophase transition of the N*-LCs of CNs suspension before and after in situ polymerization of aniline (ANI) by polarizing optical microscopy. The structure of nanocomposites of PANI/CNs was investigated at a microscopic level using Fourier transform infrared spectroscopy and X-ray diffraction. Influence of the CNs-to-ANI ratio on the morphology of the nanocomposites was also investigated at macroscopic level by scanning electron and transmission electron microscopies. It is found that the weight ratio of CNs to aniline in the suspension significantly influenced the size of the PANI particles and interaction between CNs and PANI. Moreover, electrical properties of the obtained PANI/CNs films were studied using standard four-probe technique. It is expected that the lyotropic N*-LCs of CNs might be available for an asymmetric reaction field to produce novel composites of conjugated materials.


2006 ◽  
Vol 519-521 ◽  
pp. 1341-1348 ◽  
Author(s):  
Sybrand van der Zwaag ◽  
E. Anselmino ◽  
A. Miroux ◽  
David J. Prior

To obtain further progress and a more detailed understanding of the mechanisms involved in recrystallisation, new and more accurate techniques such as in-situ observations are necessary. This innovative method has been used to monitor the recrystallisation process in a FEGSEM equipped with hot stage. Observations are done in backscatter mode with particular attention to orientation contrast. EBSD maps of the observed areas can be acquired before and after recrystallisation. Details of the movement of the interfaces between the recrystallised region and the parent structure are recorded and analysed. The results show that the grain boundaries observed do not move smoothly but with a jerky motion. The recrystallising front sweeps through small areas, corresponding to single sub-grains or small groups of them, very rapidly and then stops at other sub-grain boundaries for varying time before progressing to the following area.


2006 ◽  
Vol 28 (4) ◽  
pp. 151-159
Author(s):  
Elna Moerland ◽  
Rens L. H. P. M. van Hezik ◽  
Toine C. J. M. van der Aa ◽  
Mike W. P. M. van Beek ◽  
Adriaan J. C. van den Brule

In this study the detection of HER2 gene amplification was evaluated using Fluorescence In Situ Hybridization (FISH; PathVysion) in comparison with Multiplex Ligation-dependent Probe Amplification (MLPA), a PCR based technique. These two methods were evaluated on a series of 46 formalin fixed paraffin embedded breast carcinomas, previously tested for protein overexpression by HercepTest (grouped into Hercep 1+, 2+ and 3+). HER2 gene amplification (ratio ≥ 2.0) by FISH was found in 9/10, 10/30 and 0/6 in IHC 3+, 2+ and 1+/0 cases, respectively. Digitalized automated spot counting performed with recently developed CW4000 CytoFISH software was 100% concordant with manual FISH scoring. Using MLPA 18/46 samples showed a clear HER2 amplification. Comparing MLPA and IHC showed the same results as for FISH and IHC. All but one FISH positive cases (18/19) were confirmed by MLPA for the presence of the gene amplification. The overall concordance of detection of Her2 gene amplification by FISH and MLPA was 98% (45/46). Furthermore, both the level of amplification and equivocal results correlated well between both methods. In conclusion, MLPA is a reliable and reproducible technique and can be used as an either alternative or additional test to determine HER2 status in breast carcinomas.


2018 ◽  
Vol 2 (4) ◽  
pp. 24 ◽  
Author(s):  
Anton Davydok ◽  
Thomas Cornelius ◽  
Zhe Ren ◽  
Cedric Leclere ◽  
Gilbert Chahine ◽  
...  

The three-point bending behavior of a single Au nanowire deformed by an atomic force microscope was monitored by coherent X-ray diffraction using a sub-micrometer sized hard X-ray beam. Three-dimensional reciprocal-space maps were recorded before and after deformation by standard rocking curves and were measured by scanning the energy of the incident X-ray beam during deformation at different loading stages. The mechanical behavior of the nanowire was visualized in reciprocal space and a complex deformation mechanism is described. In addition to the expected bending of the nanowire, torsion was detected. Bending and torsion angles were quantified from the high-resolution diffraction data.


2000 ◽  
Vol 78 (4) ◽  
pp. 350-357 ◽  
Author(s):  
Dilson E Rassier ◽  
Brian R MacIntosh

In skeletal muscle, there is a length dependence of staircase potentiation for which the mechanism is unclear. In this study we tested the hypothesis that abolition of this length dependence by caffeine is effected by a mechanism independent of enhanced Ca2+ release. To test this hypothesis we have used caffeine, which abolishes length dependence of potentiation, and dantrolene sodium, which inhibits Ca2+ release. In situ isometric twitch contractions of rat gastrocnemius muscle before and after 20 s of repetitive stimulation at 5 Hz were analyzed at optimal length (Lo), Lo - 10%, and Lo + 10%. Potentiation was observed to be length dependent, with an increase in developed tension (DT) of 78 ± 12, 51 ± 5, and 34 ± 9% (mean ± SEM), at Lo - 10%, Lo, and Lo + 10%, respectively. Caffeine diminished the length dependence of activation and suppressed the length dependence of staircase potentiation, giving increases in DT of 65±13, 53 ± 11, and 45 ± 12% for Lo - 10%, Lo, and Lo + 10%, respectively. Dantrolene administered after caffeine did not reverse this effect. Dantrolene alone depressed the potentiation response, but did not affect the length dependence of staircase potentiation, with increases in DT of 58 ± 17, 26 ± 8, and 18 ± 7%, respectively. This study confirms that there is a length dependence of staircase potentiation in mammalian skeletal muscle which is suppressed by caffeine. Since dantrolene did not alter this suppression of the length dependence of potentiation by caffeine, it is apparently not directly modulated by Ca2+ availability in the myoplasm.


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