Global DNA methylation is altered by neoadjuvant chemoradiotherapy in rectal cancer and may predict response to treatment – A pilot study

2014 ◽  
Vol 40 (11) ◽  
pp. 1459-1466 ◽  
Author(s):  
J.S. Tsang ◽  
S. Vencken ◽  
O. Sharaf ◽  
E. Leen ◽  
E.W. Kay ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Rectal Cancer ◽  
Pilot Study ◽  
Neoadjuvant Chemoradiotherapy ◽  
Response To Treatment ◽  
Global Dna Methylation

scholarly journals The Long-Term Impact of Mild Traumatic Brain Injuries on Multiple Functional Outcomes and Epigenetics: A Pilot Study with College Students

2020 ◽  
Author(s):  
Hyunhwa Lee ◽  
Sungchul Lee ◽  
Ipuna Black ◽  
Laura Salado ◽  
Jonica Estrada ◽  
...  
Keyword(s):  
College Students ◽  
Dna Methylation ◽  
Pilot Study ◽  
Visual Function ◽  
Postural Balance ◽  
Sleep Disturbances ◽  
Global Dna Methylation ◽  
Balance Performance ◽  
Global Methylation

People who suffer a mild traumatic brain injury (mTBI) have heterogeneous symptoms and disease trajectories, which make it difficult to precisely diagnose and assess complications long-term. Insufficient information is available regarding how to precisely diagnose and assess mTBI. This study identified and compared deficits in cognitive, psychosocial, visual functions, and balance performance between college students with and without histories of mTBI. Global DNA methylation ratio (5-mC%) in blood was also compared as a peripheral epigenetic marker. Twenty-five volunteers participated in this pilot study, including 11 mTBI cases (27.3% females; mean age of 28.7 years, SD=5.92) and 14 healthy controls (64.3% females; mean age of 22.0, SD=4.13). All the participants were assessed for cognitive (by NIH toolbox—executive function, memory, and processing speed), psychological (by PROMIS—depression, anxiety, and sleep disturbances), visual function (by King-Devick and binocular accommodative tests), postural balance performance (by a force plate), and blood 5-mC% (global methylation) levels. Students with mTBI reported significantly poorer episodic memory, severe anxiety, and more sleep disturbance problems. They also had higher blood 5-mC% level (all p’s<.05). No significant differences were found in visual function and postural balance. These findings validate changes in cognitive, psychosocial, and global DNA methylation long after mTBI.

scholarly journals Epigenetics in Schizophrenia: A Pilot Study of Global DNA Methylation in Different Brain Regions Associated with Higher Cognitive Functions

2016 ◽  
Vol 7 ◽  
Author(s):  
Raúl Alelú-Paz ◽  
Francisco J. Carmona ◽  
José V. Sanchez-Mut ◽  
Ariel Cariaga-Martínez ◽  
Ana González-Corpas ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Pilot Study ◽  
Cognitive Functions ◽  
Brain Regions ◽  
Global Dna Methylation ◽  
Higher Cognitive Functions

Genomic characterization of rectal cancer and molecular determinants of response to neoadjuvant chemoradiotherapy.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 192-192
Author(s):  
Walid Khaled Chatila ◽  
Michael Marco ◽  
Xuan Qu ◽  
Henry S. Walch ◽  
Anisha Luthra ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Exome Sequencing ◽  
Anal Verge ◽  
Locally Advanced ◽  
Tumor Biology ◽  
Neoadjuvant Chemoradiotherapy ◽  
Response To Treatment ◽  
Primary Tumors ◽  
Response To Chemotherapy ◽  
Molecular Determinants

192 Background: Rectal cancers are clinically different from colon cancers and have not yet been molecularly characterized due to the scarcity of pretreatment specimens. Discovery of molecular determinants of response to chemotherapy and radiation in patients with locally advanced rectal cancer (LARC, stage II and III) are needed to select those who can avoid surgery and benefit from watch-and-wait strategies. Methods: We profiled 371 pre-treatment specimens using targeted-exome sequencing of 468 cancer genes (n = 325), whole-exome sequencing (n = 100), and RNA-sequencing (n = 113). The targeted-sequencing cohort included patients with stage I (n = 44), II (n = 41), III (n = 176), and IV (n = 64) disease. Primary tumors were divided into lower (LR: 0-4 cm to anal verge, n = 62), middle (MR: 4-8 cm, n = 115), and upper rectum (UR: 8-12 cm, n = 107). We examined molecular determinants of complete response (CR) and relapse free survival (RFS) in LARC patients treated with chemoradiotherapy only (CRT: n = 39), induction chemotherapy + CRT (INCT: n = 87) and consolidation chemotherapy after CRT (CCNT: n = 63). Results: Among MSS cases, oncogenic gene and signaling pathway alterations did not vary by clinical stage. WNT pathway alterations, driven by APC mutations, were more frequent in the UR (89% UR v 86% MR v 60% LR, p < 0.001) while RTK/RAS alterations were more frequent in the LR (54% UR v 69% MR v 72% LR, p < 0.03). A set of genes enriched in mTOR signaling, G2M checkpoint, EMT transition, and DNA repair were overexpressed in the UR (FDR < 0.1). The 5-yr RFS rate for LARC was 75% (CI: 68%-82%) and 24% of the cases had a CR (n = 45). MSI cases had a higher rate of CR compared to MSS cases (50% v 23%, p = 0.07) and none relapsed (n = 8). KRAS-altered MSS tumors exhibited worse RFS in cases treated with CNCT (5-yr: 74% v 97%, p = 0.01), but not in cases treated with INCT (5-yr: 67% v 72%, p = 0.7). Conclusions: WNT alterations are more frequent in the UR while RTK/RAS alterations are more frequent in the LR, suggesting differences in tumor biology between proximal and distal rectal cancer. Further, we report correlations between distinct molecular profiles and response to treatment paradigms that could guide the design of future clinical trials.

Pilot study of modified FOLFOX6 adjuvant chemotherapy for high-risk rectal cancer treated with neoadjuvant chemoradiotherapy

2015 ◽  
Vol 76 (1) ◽  
pp. 29-34
Author(s):  
Soo Jung Lee ◽  
Byung Woog Kang ◽  
Yee Soo Chae ◽  
Seung Hyun Cho ◽  
Hye Jin Kim ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Pilot Study ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Neoadjuvant Chemoradiotherapy ◽  
Modified Folfox6

Beyond the dyad: the role of mother and father in newborns’ global DNA methylation during the first month of life—a pilot study

2020 ◽  
Author(s):  
Gaia Romana Pellicano ◽  
Valeria Carola ◽  
Silvia Bussone ◽  
Marco Cecchini ◽  
Renata Tambelli ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Pilot Study ◽  
Global Dna Methylation
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