scholarly journals Does dihydropyrimidine dehydrogenase level modify plasma antioxidant capacity in colorectal cancer patients treated with fluoropyrimidines? 

Folia Medica ◽  
2021 ◽  
Vol 63 (5) ◽  
pp. 760-767
Author(s):  
Velko Minchev ◽  
Nadya Hristova-Avakumova ◽  
Kalina Kamenova ◽  
Liliya Atanasova ◽  
Marin Angelov ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Antioxidant Capacity ◽  
Cancer Patients ◽  
Statistical Significance ◽  
Dihydropyrimidine Dehydrogenase ◽  
Cancer Type ◽  
Reducing Ability ◽  
Plasma Antioxidant Capacity ◽  
Colorectal Cancer Patients ◽  
Plasma Antioxidant

Introduction: Colorectal cancer is the third most common cancer type worldwide. Fluoropyrimidines and their prodrug-based regimens are widely applied as primary medications. The main enzyme responsible for the rate-limiting step in pyrimidine and for the 5-fluorouracil catabolism is dihydropyrimidine dehydrogenase (DPD). Aim: We aimed to screen DPD level and the changes of plasma antioxidant capacity of colorectal cancer patients on 5-fluorouracil regimen.  Materials and methods: Human DPD Elisa Kit based on sandwich enzyme-linked immune-sorbent assay and spectrophotometric methods (FRAP and ABTS) were used in the study. Results: No statistically significant changes in plasma scavenging activity according to the results obtained in the ABTS system have been observed after evaluating all patients and considering DPD concentration. A decrease of the ferric reducing ability of patients’ plasma taken after the administered treatment was found. The increase of DPD level is accompanied by a decrease in the p values and therefore the statistical significance of the differences increases. Conclusions: Based on the aforementioned observations, it could be concluded that some aspects of plasma antioxidant capacity and individuals’ antioxidant status might be involved in the pathogenesis of the disease and could be altered by the activity of some enzymes. The cancer therapy in question, by the specificity of its mechanism of action, can modify patient’s oxidative status.

Exploration of the MSI landscape in Chinese pan-cancer patient by Next-Generation Sequencing.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14576-e14576
Author(s):  
Xinlu Liu ◽  
Jiasheng Xu ◽  
Jian Sun ◽  
Deng Wei ◽  
Xinsheng Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Correlation Analysis ◽  
Cancer Patients ◽  
Cancer Type ◽  
Multiple Tumor ◽  
Treatment Plans ◽  
Cancer Types ◽  
Chinese Cancer Patients ◽  
Colorectal Cancer Patients ◽  
Pan Cancer

e14576 Background: Clinically, MSI had been used as an important molecular marker for the prognosis of colorectal cancer and other solid tumors and the formulation of adjuvant treatment plans, and it had been used to assist in the screening of Lynch syndrome. However, there were currently few reports on the incidence of MSI-H in Chinese pan-cancer patients. This study described the occurrence of MSI in a large multi-center pan-cancer cohort in China, and explored the correlation between MSI and patients' TMB, age, PD-L1 expression and other indicators. Methods: The study included 8361 patients with 8 cancer types from multiple tumor centers. Use immunohistochemistry to detect the expression of MMR protein (MLH1, MSH2, MSH6 and PMS2) in patients with various cancer types to determine the MSI status and detect the expression of PD-L1 in patients. Through NGS technology, 831 genes of 8361 Chinese cancer patients were sequenced and the tumor mutation load of the patients was calculated. The MSI mutations of patients in 8 cancer types were analyzed and the correlation between MSI mutations of patients and the patient's age, TMB and PD-L1 expression was analyzed. Results: The test results showed that MSI patients accounted for 1.66% of pan-cancers. Among them, MSI-H patients accounted for the highest proportion in intestinal cancer, reaching 7.2%. The correlation analysis between MSI and TMB was performed on patients of various cancer types. The results showed that: in each cancer type, MSI-H patients had TMB greater than 10, and 26.83% of MSI-H patients had TMB greater than 100 in colorectal cancer patients. The result of correlation analysis showed that there was no significant correlation between the patient's age and the risk of MSI mutation ( P> 0.05). In addition to PAAD and LUAD, the expression of PD-L1 in MSI-H patients was higher than that in MSS patients in other cancer types( P< 0.05). The correlation analysis between PD-L1 expression and TMB in patients found that in colorectal cancer, the higher the expression of PD-L1, the higher the patient's TMB ( P< 0.05). Conclusions: In this study, we explored the incidence of MSI-H in pan-cancer patients in China and found that the TMB was greater than 10 in patients with MSI-H. Compared with MSS patients, MSI-H patients have higher PD-L1 expression, and the higher the PD-L1 expression in colorectal cancer, the higher the TMB value of patients.

scholarly journals Tegafur–uracil is a safe alternative for the treatment of colorectal cancer in patients with partial dihydropyrimidine dehydrogenase deficiency: a proof of principle

2012 ◽  
Vol 4 (4) ◽  
pp. 167-172 ◽  
Author(s):  
Daniel I.G. Cubero ◽  
Felipe Melo Cruz ◽  
Patrícia Santi ◽  
Ismael Dale C.G. Silva ◽  
Auro del Giglio
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Dehydrogenase Deficiency ◽  
Dihydropyrimidine Dehydrogenase ◽  
Gene Sequencing ◽  
Severe Toxicity ◽  
Safe Alternative ◽  
Grade 3 ◽  
Colorectal Cancer Patients ◽  
Proof Of Principle

Objective: The objective of this study was to evaluate the safety of using tegafur–uracil (UFT) in colorectal cancer patients with partial dihydropyrimidine dehydrogenase (DPD) deficiency. Patients and Methods: The study included five colorectal cancer patients who presented with acute toxicity (grades 3 and 4) after being given the first cycle of chemotherapy using 5-fluorouracil. The DPD deficiency was confirmed by gene sequencing. After a full recovery from all side effects, we changed the regimen to UFT (300 mg/m2/day) associated with leucovorin (90 mg/day) for 21 days, with an empirical dose reduction of at least 10% in the first cycle. Results: We prospectively analysed 22 UFT cycles in 5 patients. We did not observe any episodes of grade 3 or 4 toxicity. The predominant toxicities were of grades 1 and 2 (nausea, vomiting and diarrhoea). Conclusion: Here, we demonstrate a complete absence of severe toxicity in all patients and cycles analysed. We believe that UFT is a safe alternative for the treatment of patients with partial DPD deficiency.

scholarly journals Dihydropyrimidine Dehydrogenase Gene Variation and Its Association with 5-Fluorouracil Toxicity in Colorectal Patients

2018 ◽  
Vol 3 (3) ◽  
pp. 65-69
Author(s):  
Ebrahim Salehifar ◽  
Mohammad Javad Abd Haghighi ◽  
Reza Negarandeh ◽  
Ghasem Janbabai ◽  
Fatemeh Safgafi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Side Effects ◽  
Cancer Patients ◽  
Dihydropyrimidine Dehydrogenase ◽  
Venous Blood ◽  
Critical Role ◽  
Optimization Method ◽  
Gene Variation ◽  
North Of Iran ◽  
Colorectal Cancer Patients

Objective: Dihydropyrimidine dehydrogenase (DPD), an enzyme translated by DPD gene (DPYD), has a critical role in the metabolism of 5-fluorouracil (5FU). In this study we aimed to investigate the frequency of the IVS14+1 G>A, 2194G>A, 2846 A>T mutations in the DPYD gene in colorectal cancer patients in north of Iran and their association with side effects of 5FU.Methods: Venous blood samples of 89 colorectal cancer patients were drawn. After the DNA extraction from nuclear cells, a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to detect the frequency of the IVS14+1 G>A and 2846 A>T mutations. Tetra-Primer ARMS PCR optimization method was used to detect the 2194 G>A mutation. Side effects were classified according to CTCAE (common terminology criteria for adverse events V. 4) and the association between different polymorphisms and side effects were evaluated.Results: Of 89 colorectal patients, the frequency of IVS14+1 G>A and 2846 A>T polymorphism was 4 (5.1%) and 1 (1.1%), respectively. The 2194 G>A polymorphism was not detected. All 4 patients were heterozygous for IVS14+1 G>A mutation, whereas the only patient with 2846 A>T polymorphism was homozygous. Some adverse effects of 5FU including diarrhea, vomiting, mucositis and stomatitis were more frequent in patients with IVS14+1 G>A polymorphism.Conclusion: The prevalence of IVS14+1 G>A mutation in our patients were relatively high and was associated with a higher occurrence of 5FU-associated toxicities.

The 2-13C-5-fluorouracil breath test (FUBT) as a novel, rapid method for assessment of dihydropyrimidine dehydrogenase (DPD) activity in cancer patients: Initial characterization and comparison to the 2-13C-uracil breath test (UraBT)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2551-2551
Author(s):  
J. Fourie ◽  
L. K. Mattison ◽  
T. E. Wood ◽  
J. A. Posey ◽  
A. Modak ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Single Dose ◽  
Oral Dose ◽  
Cancer Patients ◽  
Drug Administration ◽  
Breath Test ◽  
Dihydropyrimidine Dehydrogenase ◽  
Metabolite Formation ◽  
Colorectal Cancer Patients ◽  
Further Development

2551 Background: The UraBT is currently in development as a phenotypic test to screen for DPD deficiency. Following an oral dose of 2-13C-uracil, the UraBT shows a significant relationship between breath 13CO2 metabolite formation and plasma 2-13C-uracil and 2-13C-dihydrouracil pharmacokinetics. We herein describe a novel, potentially more clinically relevant test in which a small oral dose of 2-13C-5-fluorouracil (5-FU) is administered, followed by assessment of breath 13CO2 metabolite formation as previously described for the UraBT. We hypothesize that the FUBT can rapidly assess interindividual variability in 5-FU catabolism and predisposition to 5-FU toxicity. Methods: Over two sessions separated by a seven day washout, a single dose (6mg/kg, p.o.) of 2-13C-uracil or 2-13C-5-FU was administered to patients with stage III-IV colorectal cancer (n = 4). Subsequent to drug administration, in each session, 13CO2 catabolite formation was quantified in the breath over eight hours. In a separate investigation over two sessions separated by a seven day washout, a single dose (3mg/kg, p.o.) of 2-13C-uracil or 213C-5-FU was administered to colorectal cancer patients with previously documented severe (n=2) or moderate (n=2) 5-FU dose-related hematological/gastrointestinal toxicity. Following drug administration 13CO2 catabolite formation was quantified over eight hours. 13CO2 concentration was expressed as Delta Over Baseline (DOB) in all sessions. Results: Compared to the UraBT, the FUBT showed an increased Cmax (50.7 ± 6.6 DOB/mg vs. 36.8 ± 7.8 DOB/mg; mean ± SD) and decreased Tmax (25 ± 4 min vs. 45 ± 6 min) for 13CO2 formation (p<0.05). The FUBT was able to distinguish patients with previously reported severe and moderate 5- FU toxicity, with 13CO2 Cmax values of 35.5 ± 9.5 DOB/mg (mean ± SD) and 59.8 ± 7.3 DOB/mg, respectively. Importantly, FUBT Cmax values positively correlated with DPD activity (rs=1.00, p<0.01). Conclusions: These data lend support to further development of the FUBT as a rapid and informative test to assess DPD activity and to predict susceptibility to severe dose-related 5-FU toxicity. [CA116964] No significant financial relationships to disclose.

scholarly journals Potential of Dihydropyrimidine Dehydrogenase Genotypes in Personalizing 5-Fluorouracil Therapy Among Colorectal Cancer Patients

2013 ◽  
pp. 1 ◽  
Author(s):  
Lay Kek Teh ◽  
Sharina Hamzah ◽  
Hazwanie Hashim ◽  
Zakaria Bannur ◽  
Zainul Amiruddin Zakaria ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Dihydropyrimidine Dehydrogenase ◽  
Colorectal Cancer Patients

scholarly journals The Influence of ProbioticLactobacillus caseiin Combination with Prebiotic Inulin on the Antioxidant Capacity of Human Plasma

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Paulina Kleniewska ◽  
Arkadiusz Hoffmann ◽  
Ewa Pniewska ◽  
Rafał Pawliczak
Keyword(s):  
Antioxidant Capacity ◽  
Human Plasma ◽  
Antioxidant Properties ◽  
Positive Influence ◽  
Reducing Ability ◽  
Plasma Antioxidant Capacity ◽  
Synbiotic Supplementation ◽  
Plasma Antioxidant ◽  
And Control ◽  
Gpx Activity

The aim of the present study was to assess whether probiotic bacteriaLactobacillus casei(4 × 108 CFU) influences the antioxidant properties of human plasma when combined with prebiotic Inulin (400 mg). Experiments were carried out on healthy volunteers (n=32). Volunteers were divided according to sex (16 male and 16 female) and randomly assigned to synbiotic and control groups. Blood samples were collected before synbiotic supplementation and after 7 weeks, at the end of the study. Catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) activity, and the ferric reducing ability of plasma (FRAP) in human plasma were examined. The administration of synbiotics containingL. caseiplus Inulin resulted in a significant increase in FRAP values (p=0.00008) and CAT activity (p=0.02) and an insignificant increase in SOD and GPx activity compared to controls. Synbiotics containingL. casei(4 × 108 CFU) with prebiotic Inulin (400 mg) may have a positive influence on human plasma antioxidant capacity and the activity of selected antioxidant enzymes.

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