IMPROVE Intervention Trial Implementing Non-invasive Circulating Tumor DNA Analysis to Optimize the Operative and Postoperative Treatment for Patients With Colorectal Cancer
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Cancer,Colorectal Neoplasms,Circulating Tumor Dna,Adjuvant Chemotherapy,Progression Free Survival
PROVIDER: 2290096 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Several organisms belonging to diverse animal groups have retained Dnmt2 as their only bona fide DNA methyltransferase gene. However, recent studies have shown that Dnmt2 functions as a tRNA methyltransferase, which prompted us to analyze the methylomes of Dnmt2-only organisms at single-base resolution. Using whole-genome bisulfite sequencing we show here that the genomes of Schistosoma mansoni and Drosophila melanogaster lack detectable DNA methylation patterns. Residual unconverted cytosine residues shared many attributes with bisulfite deamination artifacts and were observed at comparable levels in a Dnmt2-deficient fly strain. Furthermore, genetically modified mouse embryonic stem cells that had retained Dnmt2 as their only bona fide DNA methyltransferase gene, did not show any detectable DNA methylation patterns. Our results thus uncover fundamental differences among animal methylomes and suggest that Dnmt2-only organisms lack biologically relevant DNA methylation patterns.
2013-05-06 | GSE42170 | GEO
Project description:Several organisms belonging to diverse animal groups have retained Dnmt2 as their only bona fide DNA methyltransferase gene. However, recent studies have shown that Dnmt2 functions as a tRNA methyltransferase, which prompted us to analyze the methylomes of Dnmt2-only organisms at single-base resolution. Using whole-genome bisulfite sequencing we show here that the genomes of Schistosoma mansoni and Drosophila melanogaster lack detectable DNA methylation patterns. Residual unconverted cytosine residues shared many attributes with bisulfite deamination artifacts and were observed at comparable levels in a Dnmt2-deficient fly strain. Furthermore, genetically modified mouse embryonic stem cells that had retained Dnmt2 as their only bona fide DNA methyltransferase gene, did not show any detectable DNA methylation patterns. Our results thus uncover fundamental differences among animal methylomes and suggest that Dnmt2-only organisms lack biologically relevant DNA methylation patterns. Whole methylome analysis of Mus musculus. One sample was analyzed containing DNA from Dnmt1-/-, Dnmt3a-/- and Dnmt3b-/- mice.
2013-05-06 | E-GEOD-42170 | biostudies-arrayexpress
Project description:ImportanceChronic, non-cancer pain affects approximately 20-30% of the population in North America, Europe, and Australia, with surgery and trauma frequently cited as inciting events. Prospective studies of fracture patients have demonstrated an association between somatic pre-occupation, poor coping, and low recovery expectations following surgery with persistent pain, functional limitations, and lower rates of return to work. Psychological interventions, such as cognitive behavioural therapy (CBT), that are designed to modify unhelpful beliefs and behaviours have the potential to reduce persistent post-surgical pain and its associated effects among trauma patients.ObjectiveTo determine whether online CBT, versus usual care, reduces the prevalence of moderate to severe persistent post-surgical pain among participants with an open or closed fracture of the appendicular skeleton.Design, setting, and participantsThe Cognitive Behavioural Therapy to Optimize Post-Operative Fracture Recovery (COPE) protocol will be followed to conduct a multi-centre randomized controlled trial. Participants undergoing surgical repair of a long bone fracture will be randomized to receive either (1) online CBT modules with asynchronous therapist feedback or (2) usual care. The primary outcome will be the prevalence of moderate to severe persistent post-surgical pain over 12 months post-fracture. Secondary outcomes include the Short Form-36 Physical and Mental Component Summary scores, return to function, pain severity and pain interference over 12 months post-fracture, and the proportion of patients prescribed opioid class medications (and average dose) at 6 and 12 months post-fracture. The COPE trial will enroll 1000 participants with open and closed fractures of the appendicular skeleton from approximately 10 hospitals in North America.DiscussionIf CBT is effective in improving outcomes among patients with traumatic fractures, our findings will promote a new model of care that incorporates psychological barriers to recovery.Trial registrationClinicalTrials.gov Identifier: NCT04274530. Registered on 14 February 2020.
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Project description:Primary objectives: The main clinical hypothesis is that patients having undergone radical resection from CRC do not present with detectable tumor DNA in the plasma, whereas patients with detectable tumor DNA two weeks’ post-surgery have residual microscopic disease, and consequently a high risk of diseases recurrence which can be prevented with adjuvant chemotherapy.
The primary aim of the present study is to investigate – in a randomized trial - if use of standard adjuvant chemotherapy therapy improves the disease free survival in patients with molecular biological residual disease where adjuvant chemotherapy is not standard treatment
Primary endpoints: • Disease free survival at 3 year
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Project description:We find that in invasive HMLE-Twist-ER cells, SMARCE1 binds to ILF3 and is localized to ILF motifs. In contrast, ILF motifs were not enriched at SMARCE1-bound sites in noninvasive HMLE-Twist-ER cells or at SMARCC1-bound sites.
2017-03-23 | GSE96933 | GEO
Project description:The Cox-Maze procedure (CMP) for the surgical treatment of atrial fibrillation (AF) traditionally has required a median sternotomy and cardiopulmonary bypass. This study describes a method using ablation technologies to create the full Cox-Maze lesion set through a 5- to 6-cm right minithoracotomy.Twenty-two consecutive patients underwent a CMP through a right mini-thoracotomy and cardiopulmonary bypass. All patients were followed prospectively with electrocardiogram and 24-hour Holter monitoring at 3, 6, and 12 months. The CMP lesion set was created using bipolar radiofrequency energy and cryotherapy.There was no operative mortality or major complications.Two patients required a permanent pacemaker. Five patients (23%) had early atrial tachyarrhythmias. At last follow-up(mean, 18 ± 12 months), all the patients (n=22) were free from atrial dysrhythmias. At 3 months (n=19), 84% of patients were off antiarrhythmic drugs. At 6 months (n=18), 94% of patients were free from AF and off antiarrhythmic medications. At 12 months (n=16), 81% of patients were free from AF and off antiarrhythmic drugs and three patients remained on warfarin for a mechanical mitral valve.A full CMP can be performed through a right mini-thoracotomy with outstanding short-term results. This less invasive procedure can be offered to patients without compromising efficacy.
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Project description:The purpose of this study is to investigate the response rate of cetuximab plus irinotecan every 2 weeks in patients harboring wild-type KRAS with and without detectable EGFR-expressing metastatic CRC after failure to irinotecan in an exploratory manner.
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Project description:The overall objective of these studies are to confirm that ctDNA detected in plasma after intended curative treatment for CRC can be applied in clinical practice as a marker of subclinical residual disease and risk of recurrence.
| 2281569 | ecrin-mdr-crc
Project description:BackgroundMinimally-invasive pancreatoduodenectomy (MIPD) is fraught with the risk of complication-related deaths (LEOPARD-2), a significant volume-outcome relationship and a long learning curve. With rates of conversion for MIPD approaching 40%, the impact of these on overall patient outcomes, especially, when unplanned, are yet to be fully elucidated. This study aimed to compare peri-operative outcomes of (unplanned) converted MIPD against both successfully completed MIPD and upfront open PD.MethodsA systematic review of major reference databases was undertaken. The primary outcome of interest was 30-day mortality. Newcastle-Ottawa scale was used to judge the quality of the studies. Meta-analysis was performed using pooled estimates, derived using random effects model.ResultsSix studies involving 20,267 patients were included in the review. Pooled analysis demonstrated (unplanned) converted MIPD were associated with an increased 30-day (RR 2.83, CI 1.62- 4.93, p = 0.0002, I2 = 0%) and 90-day (RR 1.81, CI 1.16- 2.82, p = 0.009, I2 = 28%) mortality and overall morbidity (RR 1.41, CI 1.09; 1.82, p = 0.0087, I2 = 82%) compared to successfully completed MIPD. Patients undergoing (unplanned) converted MIPD experienced significantly higher 30-day mortality (RR 3.97, CI 2.07; 7.65, p < 0.0001, I2 = 0%), pancreatic fistula (RR 1.65, CI 1.22- 2.23, p = 0.001, I2 = 0%) and re-exploration rates (RR 1.96, CI 1.17- 3.28, p = 0.01, I2 = 37%) compared upfront open PD.ConclusionsPatient outcomes are significantly compromised following unplanned intraoperative conversions of MIPD when compared to successfully completed MIPD and upfront open PD. These findings stress the need for objective evidence-based guidelines for patient selection for MIPD.
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Project description:Despite cisplatin-based neoadjuvant chemotherapy (NAC) 60% of patients with muscle-invasive bladder cancer still have residual invasive disease at radical cystectomy (RC). The NAC-induced biological alterations in these cisplatin-resistant tumors remain largely unstudied. We analyzed gene expression from 133 patients with residual invasive disease after cisplatin-based NAC. H&E and immunohistochemistry were used to confirm tissue sampling and gene expression analysis. Established molecular subtyping models proved to be inconsistent in their classification of the post-NAC samples. Unsupervised consensus clustering revealed four distinct consensus clusters (CC). The CC1-Basal and CC2-Luminal subtypes expressed genes consistent with a basal-like and a luminal-like phenotype, respectively. The CC3-Immune subtype had the highest immune activity, including T-cell infiltration and checkpoint molecule expression, but lacked both basal and luminal markers. The CC4-Scar-like subtype expressed genes associated with wound-healing/ scarring and was associated with favorable prognosis.
2019-01-01 | GSE124305 | GEO