scholarly journals ABCC9 Is Downregulated and Prone to Microsatellite Instability on ABCC9tetra in Canine Breast Cancer

2022 ◽  
Vol 8 ◽  
Author(s):  
Pan Hao ◽  
Kai-yue Song ◽  
Si-qi Wang ◽  
Xiao-jun Huang ◽  
Da-wei Yao ◽  
...  
Keyword(s):  
Microsatellite Instability ◽  
Promoter Methylation ◽  
High Frequency ◽  
Polyacrylamide Gel Electrophoresis ◽  
Benign Tumors ◽  
Breast Cancers ◽  
Normal Tissues ◽  
High Level ◽  
Degree Of Differentiation ◽  
Quantify Gene Expression

Tumorigenesis is associated with metabolic abnormalities and genomic instability. Microsatellite mutations, including microsatellite instability (MSI) and loss of heterozygosity (LOH), are associated with the functional impairment of some tumor-related genes. To investigate the role of MSI and LOH in sporadic breast tumors in canines, 22 tumors DNA samples and their adjacent normal tissues were evaluated using polyacrylamide gel electrophoresis and silver staining for 58 microsatellites. Quantitative real-time polymerase chain reaction, promoter methylation analysis and immunohistochemical staining were used to quantify gene expression. The results revealed that a total of 14 tumors (6 benign tumors and 8 breast cancers) exhibited instability as MSI-Low tumors. Most of the microsatellite loci possessed a single occurrence of mutations. The maximum number of MSI mutations on loci was observed in tumors with a lower degree of differentiation. Among the unstable markers, FH2060 (4/22), ABCC9tetra (4/22) and SCN11A (6/22) were high-frequency mutation sites, whereas FH2060 was a high-frequency LOH site (4/22). The ABCC9tetra locus was mutated only in cancerous tissue, although it was excluded by transcription. The corresponding genes and proteins were significantly downregulated in malignant tissues, particularly in tumors with MSI. Furthermore, the promoter methylation results of the adenosine triphosphate binding cassette subfamily C member 9 (ABCC9) showed that there was a high level of methylation in breast tissues, but only one case showed a significant elevation compared with the control. In conclusion, MSI-Low or MSI-Stable is characteristic of most sporadic mammary tumors. Genes associated with tumorigenesis are more likely to develop MSI. ABCC9 protein and transcription abnormalities may be associated with ABCC9tetra instability.

scholarly journals Methylation in p14ARF is Frequently Observed in Colorectal Cancer with Low-level Microsatellite Instability

2009 ◽  
Vol 37 (4) ◽  
pp. 1038-1045 ◽  
Author(s):  
K Kominami ◽  
T Nagasaka ◽  
HM Cullings ◽  
N Hoshizima ◽  
H Sasamoto ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Promoter Methylation ◽  
Dna Methyltransferase ◽  
Methylation Status ◽  
Gene Promoters ◽  
Braf Mutations ◽  
Low Level ◽  
Methylguanine Dna Methyltransferase ◽  
High Level

Colorectal cancer (CRC) can be classified as high-level microsatellite instability (MSI-H), low-level MSI (MSI-L) and microsatellite stable (MSS) depending on levels of MSI. MSI-H CRC relies on a distinct molecular pathway due to the mismatch repair (MMR) deficiency and shows methylation in multiple gene promoters. The genetic pathway leading to MSI-L is unknown, although higher levels of promoter methylation are observed in this group compared with MSS CRCs. This study explored how promoter methylation affects MSI phenotype, by analysing the methylation status of eight CRC-related promoters, MSI phenotype and KRAS/BRAF mutations in a series of 234 CRCs. Promoter methylation of p14ARF was significantly related to MSI-L CRC with KRAS mutation. The MSI-H phenotype was related to methylation of MLH1 as expected, while the MSS phenotype was related to methylation of p16INK4a and O6-methylguanine-DNA methyltransferase, although this was not statistically significant. Thus, promoter methylation of p14ARF could be a significant alteration leading to CRC with MSI-L.

scholarly journals Lactate Dehydrogenase-B Is Silenced by Promoter Methylation in a High Frequency of Human Breast Cancers

PLoS ONE ◽  
2013 ◽  
Vol 8 (2) ◽  
pp. e57697 ◽  
Author(s):  
Nicola J. Brown ◽  
Sue E. Higham ◽  
Branko Perunovic ◽  
Mohammad Arafa ◽  
Sabapathy Balasubramanian ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Promoter Methylation ◽  
High Frequency ◽  
Breast Cancers ◽  
Human Breast

Radiotherapy for Brain Tumors: Current Practice and Future Directions

2020 ◽  
Vol 16 (3) ◽  
pp. 182-195
Author(s):  
Sarah Baker ◽  
Natalie Logie ◽  
Kim Paulson ◽  
Adele Duimering ◽  
Albert Murtha
Keyword(s):  
Brain Tumors ◽  
Treatment Strategies ◽  
Brain Parenchyma ◽  
Benign Tumors ◽  
Tumor Control ◽  
Normal Brain ◽  
Neurocognitive Deficits ◽  
Close Proximity ◽  
Recent Developments ◽  
High Level

Radiotherapy is an important component of the treatment for primary and metastatic brain tumors. Due to the close proximity of critical structures and normal brain parenchyma, Central Nervous System (CNS) radiotherapy is associated with adverse effects such as neurocognitive deficits, which must be weighed against the benefit of improved tumor control. Advanced radiotherapy technology may help to mitigate toxicity risks, although there is a paucity of high-level evidence to support its use. Recent advances have been made in the treatment for gliomas, meningiomas, benign tumors, and metastases, although outcomes remain poor for many high grade tumors. This review highlights recent developments in CNS radiotherapy, discusses common treatment toxicities, critically reviews advanced radiotherapy technologies, and highlights promising treatment strategies to improve clinical outcomes in the future.

scholarly journals Molecular aspects of high-level resistance to sulbactam-cefoperazone in Klebsiella oxytoca clinical isolates.

1996 ◽  
Vol 40 (9) ◽  
pp. 1988-1994 ◽  
Author(s):  
K Kimura ◽  
Y Arakawa ◽  
S Ohsuka ◽  
H Ito ◽  
K Suzuki ◽  
...  
Keyword(s):  
Klebsiella Oxytoca ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Point Of View ◽  
Clinical Isolates ◽  
Beta Lactamase ◽  
Beta Lactamases ◽  
Molecular Aspects ◽  
High Level ◽  
Level Resistance

Nine Klebsiella oxytoca strains which demonstrated resistance to the combination of sulbactam and cefoperazone were isolated from geographically separate hospitals in Japan in 1995. Among them, K. oxytoca SB23 showed high-level resistance to sulbactam-cefoperazone (MIC > 128 micrograms/ml) and aztreonam (MIC, 128 micrograms/ml). The sulbactam-cefoperazone resistance was not transferred from strain SB23 to Escherichia coli CSH2 by conjugation, beta-Lactamase RbiA, produced by strain SB23, was purified, and the molecular mass was estimated to be 29 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Kinetic parameters for RbiA revealed that cefoperazone and aztreonam were hydrolyzed efficiently by this enzyme. Moreover, ceftazidime and imipenem were also hydrolyzed weakly by RbiA, although strain SB23 did not show any resistance to these agents. Clavulanate, sulbactam, and tazobactam failed to block the hydrolysis of cefoperazone by RbiA. The structural gene of RbiA (blaRBI) was cloned and sequenced, and the deduced amino acid sequence of RbiA demonstrated high-level similarities to those of the beta-lactamases found in K. oxytoca D488, E23004, and plasmid-mediated MEN-1, which have been classified into Bush functional group 2be. Although RbiA demonstrates high-level molecular similarity to the enzymes in group 2be, from an enzymological point of view, this enzyme might be differentiated from the enzymes in that group. Hybridization analysis revealed that beta-lactamase genes highly similar to blaRBI were generally encoded on the chromosome of the sulbactam-cefoperazone-resistant clinical isolates of K. oxytoca tested in the study, despite their different derivations. This observation suggests that sulbactam-cefoperazone-resistant A. oxytoca strains which produce RbiA-type beta-lactamases have been proliferating in many hospitals in Japan.

scholarly journals Microsatellite genotyping from faeces of Lontra longicaudis from southern Brazil

2009 ◽  
Vol 99 (1) ◽  
pp. 5-11 ◽  
Author(s):  
Laura I. Weber ◽  
Cintia G. Hildebrand ◽  
Anderson Ferreira ◽  
Gustavo Pedarassi ◽  
José A. Levy ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Conservation Status ◽  
Significant Degree ◽  
Southern Brazil ◽  
High Genetic Diversity ◽  
Low Degree ◽  
Faecal Samples ◽  
High Level ◽  
Degree Of Differentiation ◽  
Lontra Longicaudis

A genetic study of the neotropical river otter Lontra longicaudis (Olfers, 1818), which has an unknown conservation status, was carried out at the Taim Ecological Station and the margins of the Vargas stream, Rio Grande do Sul, southern Brazil. Faecal samples were collected, and DNA was extracted using a silica-guanidine method. Five microsatellite loci were amplified using PCR with heterologous primers previously described for Lutra lutra (Linnaeus, 1758). Sixteen faecal samples out of 29 from Taim and 11 out of 14 from Vargas stream margins contained enough DNA for genetic analysis. A total of 49 different alleles were found at both localities, from which 18 were exclusively found in individuals from Taim and 17 were exclusives from Vargas individuals. The most common allele was the same at both locations for three loci (Lut715, Lut733, and Lut818). A high level of genetic diversity was found at both sites (NeTaim=4.1, HoTaim=0.299, HeTaim=0.681; NeVargas=4.9, HoVargas=0.355, HeVargas=0.724), being higher at the Vargas stream site. A high and significant level of heterozygote deficiency was observed at most loci according to the χ2 test. The homogeneity χ2 test (P<0.001) showed that there were significant differences in the allele frequencies between the two locations. Genotyping for more than one locus was possible in 81.5% of samples, from which only 37% were possible to genotype for more than three loci. A low degree of relatedness was found among individuals from Taim (R=0.055±0.310), but an even lower value of relatedness was found at the Vargas site (R= -0.285±0.440). The significant degree of differentiation (I=0.890; F ST=0.059) found between Taim and Vargas individuals suggests that there is more than one population of otters in the southern extreme of Brazil, which probably are associated with the water body systems found in this region, the Mirim and the Caiuvá/Flores/Mangueira Lagoons. The high genetic diversity and low relatedness found at the Vargas stream, lead us to believe that the Vargas stream may be acting as a corridor between these water bodies for otter dispersion.

Sign in / Sign up

Export Citation Format

Share Document