scholarly journals Circadian and chemotherapy-related changes in urinary modified nucleosides excretion in patients with metastatic colorectal cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
S. Dulong ◽  
Q. Huang ◽  
P. F. Innominato ◽  
A. Karaboue ◽  
M. Bouchahda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Urinary Excretion ◽  
Metastatic Colorectal Cancer ◽  
Cellular Proliferation ◽  
Activity Rhythm ◽  
Modified Nucleosides ◽  
Non Invasive ◽  
Circadian Control ◽  
Colorectal Cancer Patients ◽  
Rest Activity

AbstractUrinary levels of modified nucleosides reflect nucleic acids turnover and can serve as non-invasive biomarkers for monitoring tumour circadian dynamics, and treatment responses in patients with metastatic colorectal cancer. In 39 patients, median overnight urinary excretion of LC-HRMS determinations of pseudouridine, was ~ tenfold as large as those of 1-methylguanosine, 1-methyladenosine, or 4-acetylcytidine, and ~ 100-fold as large as those of adenosine and cytidine. An increase in any nucleoside excretion after chemotherapy anticipated plasma carcinoembryonic antigen progression 1–2 months later and was associated with poor survival. Ten fractionated urines were collected over 2-days in 29 patients. The median value of the rhythm-adjusted mean of urinary nucleoside excretion varied from 64.3 for pseudouridine down to 0.61 for cytidine. The rhythm amplitudes relative to the 24-h mean of 6 nucleoside excretions were associated with rest duration, supporting a tight link between nucleosides turnover and the rest-activity rhythm. Moreover, the amplitude of the 1-methylguanosine rhythm was correlated with the rest-activity dichotomy index, a significant predictor of survival outcome in prior studies. In conclusion, urinary excretion dynamics of modified nucleosides appeared useful for the characterization of the circadian control of cellular proliferation and for tracking early responses to treatments in colorectal cancer patients.

scholarly journals Inter- and intra-patient circadian variabilities in eight urinary modified nucleosides excretion in patients with metastatic colorectal cancer

2019 ◽  
Author(s):  
Sandrine Dulong ◽  
Huang Qi ◽  
Innominato Pasquale Fabio ◽  
Karaboue Abdoulaye ◽  
Bouchahda Mohamed ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Urinary Excretion ◽  
Cellular Proliferation ◽  
Modified Nucleosides ◽  
Activity Data ◽  
Medical Treatments ◽  
Non Invasive ◽  
R1 Resection ◽  
Circadian Timing System ◽  
Colorectal Cancer Patients

Abstract Background : Modified nucleosides reflect nucleic acids turnover, and are eliminated into the urine. They can serve as non-invasive biomarkers for monitoring tumour dynamics, and treatment responses. Methods : 8 modified nucleosides were determined by LC-HRMS in urine voids collected in three linical trials recorded on NCT01693848, NCT01693861 and NCT01693835 by a total of 39 patients. The patients’ circadian timing system was studied by wrist actimetry. Rhythms parameters were estimated using Hidden Markov model (HMM) for telemetric activity data and cosinor analysis for urinary nucleosides excretion. Results : Pseudouridine, was ~ 10-fold larger than those of 1-methylguanosine, 1-methyladenosine, or 4-acetylcytidine, and ~100 fold larger than those of adenosine and cytidine. In St 1, a significant increase in the overnight urinary excretion of 1-methylguanosine was associated with prolonged 4-year survival in patients with R1 resection for liver metastases. In St 2, a significant increase in one nucleoside excretion after chemotherapy was associated with that in plasma carcinoembryonic antigen 1-2 months later, and poor survival. In St3, ten fractionated urines were collected over 2-days. Circadian and/or 12-h rhythms were found in up to 48.3% of the patients for pseudouridine. Rhythm amplitudes were significantly associated with rest-activity circadian parameters. Conclusion : Urinary excretion dynamics of modified nucleosides appeared useful for tracking early responses to surgical or medical treatments, and for characterizing circadian control of cellular proliferation in colorectal cancer patients.

Circadian rest-activity rhythm as a predictor of survival in metastatic colorectal cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14006-e14006 ◽  
Author(s):  
David Spiegel ◽  
Pierre-Antoine Dugué ◽  
Pasquale F. Innominato ◽  
Abdoulaye Karaboué ◽  
Garance Dispersyn ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Progression ◽  
Activity Rhythm ◽  
Performance Status ◽  
Progression Free Survival ◽  
Adjusted Relative Risk ◽  
Circadian Timing System ◽  
Metastatic Sites ◽  
Rest Activity

e14006 Background: Experimental disruption of the Circadian Timing System (CTS) accelerates cancer progression. The relative amount of activity in-bed versus out-of-bed (I<O) was identified as a quantitative CTS estimate that predicted survival in two cohorts of patients with metastatic colorectal cancer (CI, CII). Methods: The independent prognostic value of I<O was investigated for Overall Survival (OS) and Progression-Free Survival (PFS) 1) in a new cohort of 142 patients (CIII) receiving circadian-based salvage treatment for metastatic colorectal cancer, and 2) in a pooled population of 436 patients from cohorts I-III. All patients had two-day rest-activity rhythm monitoring and then received a new treatment. Cohort-adjusted data were analyzed with log rank and multivariate Cox analyses. Results: Patients in CIII had poor prognosis disease compared to CI and CII, as assessed by prior chemotherapy (CIII, 69%; CI, 59.5%; CII, none), prior oxaliplatin (CIII, 55%; CII, none; CI, 2%) and/or irinotecan (CIII, 39.4%; CII, none; CI, 7%). The 273 male and 163 female patients in the pooled population had generally good performance status 0 (60.7%) or 1 (33.1%) and 51% had two or more metastatic sites. Following rest-activity rhythm determination, patients received a median of 8 chemotherapy courses. Median OS was 21.6 months [95% Confidence Limits, 17.8 to 25.5] in the patients with I<O above the cutoff median value of 97.5% as compared to 11.9 months [10.4 to 13.3] in those with a lower I<O (p from Log rank < 0.001). The adjusted relative risk related to I<O above cutoff was 0.587 [0.477 to 0.722] for earlier death (p<0.001) and 0.661 [0.542 to 0.807] for earlier progression (p <0.001). Conclusions: The circadian biomarker indicator I<O is a robust and independent quantitative long-term predictor of both OS and PFS in patients with metastatic colorectal cancer. Cancer patients with low I<O could potentially benefit from specific treatments for circadian disruption in order to enhance survival.

scholarly journals Influence of Postoperative Changes in Sarcopenia on Long-Term Survival in Non-Metastatic Colorectal Cancer Patients

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2410
Author(s):  
Chungyeop Lee ◽  
In-Ja Park ◽  
Kyung-Won Kim ◽  
Yongbin Shin ◽  
Seok-Byung Lim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Medical Center ◽  
The Body ◽  
Term Survival ◽  
Postoperative Changes ◽  
Asan Medical ◽  
Colorectal Cancer Patients

The effect of perioperative sarcopenic changes on prognosis remains unclear. We conducted a retrospective cohort study with 2333 non-metastatic colorectal cancer patients treated between January 2009 and December 2012 at the Asan Medical Center. The body composition at diagnosis was measured via abdominopelvic computed tomography (CT) using Asan-J software. Patients underwent CT scans preoperatively, as well as at 6 months–1 year and 2–3 years postoperatively. The primary outcome was the association between perioperative sarcopenic changes and survival. According to sarcopenic criteria, 1155 (49.5%), 890 (38.2%), and 893 (38.3%) patients had sarcopenia preoperatively, 6 months–1 year, and 2–3 years postoperatively, respectively. The 5-year overall survival (OS) (95.8% vs. 92.1%, hazard ratio (HR) = 2.234, p < 0.001) and 5-year recurrence-free survival (RFS) (93.2% vs. 86.2%, HR = 2.251, p < 0.001) rates were significantly lower in patients with preoperative sarcopenia. Both OS and RFS were lower in patients with persistent sarcopenia 2–3 years postoperatively than in those who recovered (OS: 96.2% vs. 90.2%, p = 0.001; RFS: 91.1% vs. 83.9%, p = 0.002). In multivariate analysis, postoperative sarcopenia was confirmed as an independent factor associated with decreased OS and RFS. Pre- and postoperative sarcopenia and changes in the condition during surveillance were associated with oncological outcomes.

scholarly journals Small EVs-Associated DNA as Complementary Biomarker to Circulating Tumor DNA in Plasma of Metastatic Colorectal Cancer Patients

2021 ◽  
Vol 14 (2) ◽  
pp. 128
Author(s):  
Silvia Galbiati ◽  
Francesco Damin ◽  
Dario Brambilla ◽  
Lucia Ferraro ◽  
Nadia Soriani ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Digital Pcr ◽  
Extracellular Vesicle ◽  
Circulating Tumor Dna ◽  
Mutation Status ◽  
Promising Practice ◽  
Colorectal Cancer Patients ◽  
Tumor Dna

It is widely accepted that assessing circular tumor DNA (ctDNA) in the plasma of cancer patients is a promising practice to evaluate somatic mutations from solid tumors noninvasively. Recently, it was reported that isolation of extracellular vesicles improves the detection of mutant DNA from plasma in metastatic patients; however, no consensus on the presence of dsDNA in exosomes has been reached yet. We analyzed small extracellular vesicle (sEV)-associated DNA of eleven metastatic colorectal cancer (mCRC) patients and compared the results obtained by microarray and droplet digital PCR (ddPCR) to those reported on the ctDNA fraction. We detected the same mutations found in tissue biopsies and ctDNA in all samples but, unexpectedly, in one sample, we found a KRAS mutation that was not identified either in ctDNA or tissue biopsy. Furthermore, to assess the exact location of sEV-associated DNA (outside or inside the vesicle), we treated with DNase I sEVs isolated with three different methodologies. We found that the DNA inside the vesicles is only a small fraction of that surrounding the vesicles. Its amount seems to correlate with the total amount of circulating tumor DNA. The results obtained in our experimental setting suggest that integrating ctDNA and sEV-associated DNA in mCRC patient management could provide a complete real-time assessment of the cancer mutation status.

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