scholarly journals Post-treatment recovery of suboptimal DNA repair capacity and gene expression levels in colorectal cancer patients

2014 ◽  
Vol 54 (9) ◽  
pp. 769-778 ◽  
Author(s):  
Jana Slyskova ◽  
Francesca Cordero ◽  
Barbara Pardini ◽  
Vlasta Korenkova ◽  
Veronika Vymetalkova ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Dna Repair ◽  
Cancer Patients ◽  
Post Treatment ◽  
Repair Capacity ◽  
Expression Levels ◽  
Dna Repair Capacity ◽  
Colorectal Cancer Patients ◽  
Gene Expression Levels

scholarly journals Female ageing affects the DNA repair capacity of oocytes in IVF using a controlled model of sperm DNA damage in mice

2020 ◽  
Vol 35 (3) ◽  
pp. 529-544 ◽  
Author(s):  
F Horta ◽  
S Catt ◽  
P Ramachandran ◽  
B Vollenhoven ◽  
P Temple-Smith
Keyword(s):  
Gene Expression ◽  
Dna Damage ◽  
Dna Repair ◽  
Age Groups ◽  
Oocyte Quality ◽  
Repair Capacity ◽  
Sperm Dna Damage ◽  
Dna Repair Capacity ◽  
Sperm Dna ◽  
Damage Response

Abstract STUDY QUESTION Does female ageing have a negative effect on the DNA repair capacity of oocytes fertilised by spermatozoa with controlled levels of DNA damage? SUMMARY ANSWER Compared to oocytes from younger females, oocytes from older females have a reduced capacity to repair damaged DNA introduced by spermatozoa. WHAT IS KNOWN ALREADY The reproductive lifespan in women declines with age predominantly due to poor oocyte quality. This leads to decreased reproductive outcomes for older women undergoing assisted reproductive technology (ART) treatments, compared to young women. Ageing and oocyte quality have been clearly associated with aneuploidy, but the range of factors that influence this change in oocyte quality with age remains unclear. The DNA repair activity prior to embryonic genomic activation is considered to be of maternal origin, with maternal transcripts and proteins controlling DNA integrity. With increasing maternal age, the number of mRNAs stored in oocytes decreases. This could result in diminished efficiency of DNA repair and/or negative effects on embryo development, especially in the presence of DNA damage. STUDY DESIGN, SIZE, DURATION Oocytes from two age groups of 30 super-ovulated female mice (young: 5–8 weeks old, n = 15; old: 42–45 weeks old, n = 15) were inseminated with sperm from five males with three different controlled DNA damage levels; control: ≤10%, 1 Gray (Gy): 11–30%, and 30 Gy: >30%. Inseminated oocytes (young: 125, old: 78) were assessed for the formation of zygotes (per oocyte) and blastocysts (per zygote). Five replicates of five germinal vesicles (GVs) and five MII oocytes from each age group were analysed for gene expression. The DNA damage response (DDR) was assessed in a minimum of three IVF replicates in control and 1 Gy zygotes and two-cell embryos using γH2AX labelling. PARTICIPANTS/MATERIALS, SETTING, METHODS Swim-up sperm samples from the cauda epididymidis of C57BL6 mice were divided into control (no irradiation) and 1- and 30-Gy groups. Treated spermatozoa were irradiated at 1 and 30 Gy, respectively, using a linear accelerator Varian 21iX. Following irradiation, samples were used for DNA damage assessment (Halomax) and for insemination. Presumed zygotes were cultured in a time-lapse incubator (MIRI, ESCO). Gene expression of 91 DNA repair genes was assessed using the Fluidigm Biomark HD system. The DNA damage response in zygotes (6–8 h post-fertilisation) and two-cell embryos (22–24 h post-fertilisation) was assessed by immunocytochemical analysis of γH2AX using confocal microscopy (Olympus FV1200) and 3D volumetric analysis using IMARIS software. MAIN RESULTS AND THE ROLE OF CHANCE The average sperm DNA damage for the three groups was statistically different (control: 6.1%, 1 Gy: 16.1%, 30 Gy: 53.1%, P < 0.0001), but there were no significant differences in fertilisation rates after IVF within or between the two age groups [(young; control: 86.79%, 1 Gy: 82.75%, 30 Gy: 76.74%) (old; control: 93.1%, 1 Gy: 70.37%, 30 Gy: 68.18%) Fisher’s exact]. However, blastocyst rates were significantly different (P < 0.0001) among the groups [(young; control: 86.95%, 1 Gy: 33.33%, 30 Gy: 0.0%) (old; control: 70.37%, 1 Gy: 0.0%, 30 Gy: 0.0%)]. Between the age groups, 1-Gy samples showed a significant decrease in the blastocyst rate in old females compared to young females (P = 0.0166). Gene expression analysis revealed a decrease in relative expression of 21 DNA repair genes in old GV oocytes compared to young GV oocytes (P < 0.05), and similarly, old MII oocytes showed 23 genes with reduced expression compared to young MII oocytes (P < 0.05). The number of genes with decreased expression in older GV and MII oocytes significantly affected pathways such as double strand break (GV: 5; MII: 6), nucleotide excision repair (GV: 8; MII: 5) and DNA damage response (GV: 4; MII: 8). There was a decreased DDR in zygotes and in two-cell embryos from old females compared to young regardless of sperm treatment (P < 0.05). The decrease in DNA repair gene expression of oocytes and decreased DDR in embryos derived from older females suggests that ageing results in a diminished DNA repair capacity. LARGE-SCALE DATA N/A LIMITATIONS, REASONS FOR CAUTION Ionising radiation was used only for experimental purposes, aiming at controlled levels of sperm DNA damage; however, it can also damage spermatozoa proteins. The female age groups selected in mice were intended to model effects in young and old women, but clinical studies are required to demonstrate a similar effect. WIDER IMPLICATIONS OF THE FINDINGS Fertilisation can occur with sperm populations with medium and high DNA damage, but subsequent embryo growth is affected to a greater extent with aging females, supporting the theory that oocyte DNA repair capacity decreases with age. Assessment of the oocyte DNA repair capacity may be a useful diagnostic tool for infertile couples. STUDY FUNDING/COMPETING INTEREST(S) Funded by the Education Program in Reproduction and Development, Department of Obstetrics and Gynaecology, Monash University. None of the authors has any conflict of interest to report.

scholarly journals Evaluation of ST13 gene expression in colorectal cancer patients

2005 ◽  
Vol 6 (12) ◽  
pp. 1170-1175 ◽  
Author(s):  
Qing-hua Dong ◽  
Shu Zheng ◽  
Yue Hu ◽  
Gong-xing Chen ◽  
Jia-yi Ding
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Cancer Patients ◽  
Colorectal Cancer Patients

scholarly journals The Influence of Tumor Microenvironment on ATG4D Gene Expression in Colorectal Cancer Patients

2018 ◽  
Vol 35 (12) ◽  
Author(s):  
Justyna Gil ◽  
David Ramsey ◽  
Pawel Pawlowski ◽  
Elzbieta Szmida ◽  
Przemyslaw Leszczynski ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Tumor Microenvironment ◽  
Cancer Patients ◽  
Colorectal Cancer Patients

scholarly journals The Effect of miR-145-5p, DANCR and NRAS Expression Levels on the Survival Rate of Colorectal Cancer Patients

2021 ◽  
Vol 22 (12) ◽  
pp. 4043-4049
Author(s):  
Fatemeh Bahreini ◽  
Masoud Saidijam ◽  
Saeid Afshar ◽  
Zahra Mousivand ◽  
Rezvan Najafi
Keyword(s):  
Colorectal Cancer ◽  
Survival Rate ◽  
Cancer Patients ◽  
Expression Levels ◽  
Colorectal Cancer Patients

Abstract 5367: DNA repair capacity, gene expression and epigenomic profiles in bladder cancer

2014 ◽  
Author(s):  
Barbara Pardini ◽  
Alessandra Allione ◽  
Simonetta Guarrera ◽  
Valentina Turinetto ◽  
Giovanni Fiorito ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bladder Cancer ◽  
Dna Repair ◽  
Repair Capacity ◽  
Dna Repair Capacity

Abstract 478: Investigating prognostic value of proinflammatory M1 gene expression in colorectal cancer patients

2019 ◽  
Author(s):  
Pankaj Ahluwalia ◽  
Chance Bloomer ◽  
Chetan Pundkar ◽  
Kimya Jones ◽  
Ashis Mondal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Colorectal Cancer Patients
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