Detection of cancer clones in human colorectal adenoma as revealed by increased DNA instability and other bio-markers

An immunohistochemical differential staining of cancerous cells with anti-cytidine antibody after denaturation of nuclear DNA by acid hydrolysis with 2N HCl at 30°C for 20 min (DNA-instability test) has been used as a marker for malignancy. The test was applied to bioptic tissues of human colorectal polyps assessed histopathologically as hyperplastic polyp (11 cases), tubular adenoma of mild (68 cases), moderate (102 cases), and severe (46 cases) dysplasia, and adenocarcinoma (30 cases). The serial sections of the same tissues were also subjected to immunohistochemical staining for Ki67, p53, DNA-fragmentation factor 45 (DFF45) and vascular endothelial growth factor (VEGF). The DNA-instability test was positive in 30 (100%) adenocarcinoma cases, 46 (100%) severe dysplasia adenoma cases, 36 (35.29%) moderate dysplasia adenoma cases, and 8 (11.76%) mild dysplasia adenoma cases, indicating malignancy. All hyperplastic polyps were negative to the DNA-instability test. Furthermore, the percentage of glands positive in the DNAinstability test steadily increased in going from mild (10%), to moderate (35%), to severe (100%) dysplasia, and adenocarcinoma (100%). All other biological markers tested in the present study showed significantly higher values in those adenoma glands that werepositive to the DNA-instability test, irrespective of the dysplasia grade, as compared to the markers in the adenoma glands that were negative to DNA instability testing. Furthermore, the former values were comparable to those in adenocarcinoma. The results indicate that cancer cell clones are already present at the adenoma stages showing positivity to DNA instability testing, enhanced proliferative activity, p53 mutation and induction of DFF45 and VEGF, at a time when the degree of morphological atypia are not yet large enough for them to be identified as cancer. These factors promote cancer cell proliferation, produce heterogeneous subclones due to DNA instability, enhance their survival by escaping apoptosis, and provide abundant nutrients by neovascularization during the early-stage progression of colorectal cancer

Microstructures and Thermoelectric Properties of Sintered Misfit-Layered Cobalt Oxide

Misfit-layered cobalt oxide Ca3Co4O9 is considered to be a prospective material for thermoelectric conversion. The thermoelectric properties are anisotropic owing to its anisotropic crystal structure. The crystal has preferred thermoelectric properties along the a-b plane. Therefore, the thermoelectric properties are improved and controlled by the degree of orientation of the sintered sample. In the present work, Sr-doped misfit cobalt oxide Ca2.7Sr0.3Co4O9 was prepared by solid-phase reaction, followed by uniaxial compression molding and sintering at 1173 K. The Seebeck coefficient α, electrical resistivity ρ, and dimensionless figure of merit ZT were measured as a function of the compression pressure applied in the uniaxial molding. α, ρ, and ZT as functions of the degree of orientation and the relative density are experimentally clarified and explained by calculations using the compound model

Detection of cancer clones in human gastric adenoma by increased DNA-instability and other biomarkers

An immunohistochemical differential staining of cancerous cells with anti-cytidine antibody after denaturation of nuclear DNA by acid hydrolysis with 2N HCl at 30°C for 20 min (DNA-instability test) has been used as a marker of malignancy. The test was applied to bioptic tissues of human gastric polyp assessed histopathologically as foveolar hyperplastic polyp (13 cases), mild (58 cases), moderate (86 cases), and severe (20 cases) dysplasia, and adenocarcinomas (14 cases). The serial sections of the same tissues were also subjected to immunohistochemical staining for Ki67, p53, DNA-fragmentation factor (DFF45), and basic fibroblast growth factor (bFGF). The DNA-instability test was positive in 14 (100%) adenocarinoma cases, 20 (100%) severe dysplasia cases, 52 (60.5%) moderate dysplasia cases, and 12 (20.7%) mild dysplasia cases, indicating malignancy. All foveolar hyperplastic polyps were negative to the DNA-instability testing. Furthermore, the percentage of glands positive in the DNA-instability test steadily increased in going from mild (10%), to moderate (40%), to severe (100%) dysplasia, and adenocarcinoma (100%). All other biological markers tested in the present study showed significantly higher values in the adenoma glands, being positive to DNA-instability testing, irrespective of the dysplasia grade, as compared to those in the adenoma glands that were negative to DNA-instability testing. Furthermore, the former values were comparable to those in adenocarcinoma. These results indicate that cancer cell clones are already present at the adenoma stages showing a positive DNA-instability test, enhanced proliferative activity, p53 mutation, induction of DFF45 and bFGF. These factors allow cancer cell proliferation, producing heterogeneous subclones due to DNA-instability, enhancing their survival by escaping apoptosis, and providing abundant nutrients during the early-stage progression of gastric cancer. Based on these findings, we herein propose the concept of “procancer” (as opposed to “precancer”) as being a unique stage during the course of carcinogenesis and cancer progression. We designate the term to cancer clones at the very early stages of malignant progression that do not show distinguishable morphological atypia but do show positive DNA-instability testing and positive staining for various biomarkers such as Ki67, p53, DFF45, and bFGF. We also define the abnormal positive staining of these biomarkers, including the DNA-instability test as “functional atypia”, compared to the ordinary morphological atypia

Synthesis, structure, and magnetic and dielectric properties of magnetoelectric BaDyFeO4 ferrite

BaDyFeO4 was prepared by a conventional solid-state method in air at 1573 K. It crystallizes in space group Pnma (No. 62) with a = 13.16861(1) angstrom, b = 5.70950(1) angstrom, and c = 10.26783(1) angstrom, and it is isostructural with BaYFe0 4 . Three magnetic transitions were found in BaDyFeO4 at T-N3 = 9 K, T-N2 = 23 K, and T-N1 =47 K in zero magnetic field in comparison with two magnetic transitions observed in BaYFeO4. Magnetic-field-induced transitions were also detected in BaDyFeO4 at 18 and 28 kOe (at T= 1.8 K). Frequency-dependent broad dielectric peaks were observed in BaDyFeO4 spanning between T-N2 and T-N and centred at 35 K - this temperature does not coincide with any T-N. No dielectric anomalies were found at T-N1 and T-N3, while very weak frequency-independent dielectric anomalies were detected at T-N2. Positive and negative magnetodielectric effects were measured in BaDyFeO4 (within a range of -0.8 and + 0.4% up to 90 kOe) reflecting magnetic-field dependence of dielectric constant. Pyroelectric current measurements did not detect any ferroelectricity in BaDyFeO4 under measurement conditions used. No dielectric anomalies and no magnetodielectric effects were found in BaYFeO4. (C) 2019 Elsevier B.V. All rights reserved

Immunohistochemical detection of early-stage carcinogenesis of oral leukoplakia by increased DNA-instability and various malignancy markers

The degree of DNA instability as determined by immunohistochemical staining with anti-singlestranded DNA antibody after acid hydrolysis (the DNAinstability test) was used as a marker of malignancy. The test was applied to tissues of oral leukoplakia assessed histopathologically as hyperplasia (38 cases), mild (12 cases), moderate (11 cases) and severe (8 cases) dysplasia, and invasive squamous cell carcinoma (SCC, 20 cases). Tissues were subjected to immunohistochemical staining for proliferating cell nuclear antigen (PCNA), p53, DNA-fragmentation factor 45 (DFF45), analysis of various AgNORs parameters, and triple immunostaining for vascular endothelial growth factor (VEGF), CD34, and PCNA. The DNA instability test was positive in 20 (100%) SCC cases, 8 (100%) severe dysplasia cases, 8 (72.7%) moderate dysplasia cases, 6 (50.0%) mild dysplasia cases, and 9 (23.7%) hyperplasia cases, indicating malignancy. The proportion of lesions positive for PCNA, p53, DFF45, and values of AgNORs parameters steadily increased from hyperplasia to mild, moderate and severe dysplasia, and SCC, especially in those showing positive DNA instability test, indicative of malignancy. Based on these results, 44.9% of leukoplakia were malignant tissues, namely carcinoma in situ. The proportion of PCNA-positive vascular endothelial cells in the vicinity of VEGF-positive epithelial lesion was significantly higher than that of negative DNA instability lesions, as revealed by immunohistochemical triple staining for VEGF, CD34, and PCNA. Our results suggest that increased DNA instability, enhanced proliferative activity, p53 mutation, and induction of DFF45 and VEGF may allow cancer cell proliferation, enhance their survival by escaping apoptosis, and provide abundant nutrients during early-stage carcinogenesis of oral leukoplakia