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Oxidative Medicine and Cellular... 2020Previous studies have disclosed the antihyperuricemic effect of polydatin, a natural precursor of resveratrol; however, the mechanisms of action still remain elusive....
Previous studies have disclosed the antihyperuricemic effect of polydatin, a natural precursor of resveratrol; however, the mechanisms of action still remain elusive. The present study was undertaken to evaluate the therapeutic effects and the underlying mechanisms of polydatin on potassium oxonate-induced hyperuricemia in rats through metabonomic technology from a holistic view. Nuclear magnetic resonance (NMR) spectroscopy was applied to capture the metabolic changes in sera and urine collected from rats induced by hyperuricemia and polydatin treatment. With multivariate data analysis, significant metabolic perturbations were observed in hyperuricemic rats compared with the healthy controls. A total of eleven and six metabolites were identified as differential metabolites related to hyperuricemia in serum and urine of rats, respectively. The proposed pathways primarily included branched-chain amino acid (BCAA) metabolism, glycolysis, the tricarboxylic acid cycle, synthesis and degradation of ketone bodies, purine metabolism, and intestinal microflora metabolism. Additionally, some metabolites indicated the risk of renal injury induced by hyperuricemia. Polydatin significantly lowered the levels of serum uric acid, creatinine, and blood urea nitrogen and alleviated the abnormal metabolic status in hyperuricemic rats by partially restoring the balance of the perturbed metabolic pathways. Our findings shed light on the understanding of the pathophysiological process of hyperuricemia and provided a reference for revealing the metabolic mechanism produced by polydatin in the treatment of hyperuricemia.
Topics: Animals; Blood Urea Nitrogen; Creatinine; Disease Models, Animal; Drugs, Chinese Herbal; Glucosides; Humans; Hyperuricemia; Kidney; Male; Metabolomics; Oxonic Acid; Rats; Rats, Sprague-Dawley; Stilbenes; Uric Acid
PubMed: 32695259
DOI: 10.1155/2020/6943860 -
World Journal of Surgical Oncology Apr 2021Adjuvant tegafur-gimeracil-oteracil (S-1) is commonly used for gastric cancer in Asia, and tegafur-uracil (UFT) is another oral fluoropyrimidine when S-1 is unavailable....
BACKGROUND
Adjuvant tegafur-gimeracil-oteracil (S-1) is commonly used for gastric cancer in Asia, and tegafur-uracil (UFT) is another oral fluoropyrimidine when S-1 is unavailable. The real-world data of adjuvant UFT has less been investigated.
METHODS
Patients with pathological stage II-IIIB (except T1) gastric cancer receiving adjuvant UFT or S-1 monotherapy after D2 gastrectomy were included. Usage of UFT or S-1 was based on reimbursement policy of the Taiwanese healthcare system. The characteristics, chemotherapy completion rates, and 5-year recurrence-free survival (RFS) and overall survival (OS), were compared between these two groups.
RESULTS
From 2005 to 2016, 86 eligible patients were included. Most tumor characteristics were similar between the UFT group (n = 37; age 59.1 ± 13.9 years) and S-1 group (n = 49; age 56.3 ± 10.7 years), except there were significantly more Borrmann type III/IV (86.5% versus 67.3%; p = 0.047) and T4 (56.8% versus 10.2%; p < 0.001) lesions in the UFT group than in the S-1 group. The chemotherapy complete rates were similar in the two groups. The 5-year RFS was 56.1% in the UFT group and 59.6% in the S-1 group (p = 0.71), and the 5-year OS was 78.3% in the UFT group and 73.1% in the S-1 group (p = 0.48). The hazard ratio of adjuvant chemotherapy (S-1 versus UFT) on RFS was 1.25 (95% confidence interval = 0.53-2.94) when Borrmann type and T and N stages were adjusted.
CONCLUSIONS
This small cohort study showed adjuvant UFT, and S-1 monotherapy had a comparable long-term outcome for pathological stage II-IIIB gastric cancer following D2 gastrectomy.
Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cohort Studies; Disease-Free Survival; Drug Combinations; Female; Humans; Middle Aged; Neoplasm Staging; Oxonic Acid; Prognosis; Stomach Neoplasms; Tegafur; Treatment Outcome; Uracil
PubMed: 33865416
DOI: 10.1186/s12957-021-02233-2 -
International Journal of Clinical... Jun 2019S-1 is an oral anticancer drug composed of tegafur (FT), which is a prodrug of 5-FU, 5-chloro-2,4-dihydroxypyridine (CDHP), and potassium oxonate. Recently, some studies...
BACKGROUND
S-1 is an oral anticancer drug composed of tegafur (FT), which is a prodrug of 5-FU, 5-chloro-2,4-dihydroxypyridine (CDHP), and potassium oxonate. Recently, some studies have been reported on watering eyes caused by S-1. However, the mechanism of watering eyes caused by S-1 is still unclear. The aim of this study was to investigate the correlation between tears and plasma concentrations of FT, 5-FU, and CDHP, which are components and active modulator of S-1.
METHODS
We prospectively investigated the pharmacokinetics (PK) of FT, 5-FU, and CDHP in plasma and in tears of gastric cancer patients who were treated with S-1 monotherapy at the dose of 80 mg/m/day. Plasma and tears from both eyes were obtained 1, 2, 4, and 8 h after S-1 administration on day 1 and 14 of the first cycle.
RESULTS
Total of eight patients were enrolled. All the FT, 5-FU and CDHP were detected both in plasma and in tears, and their PK parameters were measured. There was a positive correlation between the concentrations of FT, 5-FU and CDHP in the plasma and those in the tears on day 1 and day 14 (correlation coefficients r, right eye/left eye: r = 0.882/0.878, 0.877/0.890, and 0.885/0.878, respectively).
CONCLUSION
There was a positive correlation between the concentrations of FT, 5-FU and CDHP in the plasma and those in the tears. The result is expected to facilitate the further investigation into the causes of watering eyes and the establishment of the effective methods for the prevention and the treatment.
Topics: Adult; Aged; Drug Combinations; Female; Fluorouracil; Humans; Male; Middle Aged; Oxonic Acid; Plasma; Prospective Studies; Pyridines; Stomach Neoplasms; Tears; Tegafur; Tissue Distribution
PubMed: 31011915
DOI: 10.1007/s10147-018-01387-6 -
Journal of B.U.ON. : Official Journal... 2021To investigate the clinical efficacy and safety of apatinib combined with tegafur-gimeracil-oteracil potassium (S-1) in the second-line treatment of advanced gastric...
PURPOSE
To investigate the clinical efficacy and safety of apatinib combined with tegafur-gimeracil-oteracil potassium (S-1) in the second-line treatment of advanced gastric cancer.
METHODS
A total of 126 patients with advanced gastric cancer admitted to our hospital from January 2017 to September 2018 were enrolled as the research objects, none of whom underwent surgery. For these patients, second-line treatment was recommended due to the failure of first-line treatment. According to the different therapeutic options, patients were categorized into S-1 group (n=63) and Apatinib group (S-1 combined with apatinib, n=63), and drugs were administered orally. The clinical efficacy, serological indicators, adverse reactions and immune function were compared between the two groups. Besides, the survival status of patients was recorded through follow-up.
RESULTS
In S-1 group and Apatinib group, the objective response rate (ORR) was 30.2% (19/63) vs. 50.8% (32/63) and the disease control rate (DCR) was 54.0% (34/63) vs. 74.6% (47/63), respectively. The results indicated that Apatinib group was superior to S-1 group in terms of ORR and DCR, suggesting statistically significant differences (p=0.018, p=0.016). Compared with those before treatment, the serum levels of carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), and tumor supplied group of factors (TSGF) in the two groups of patients were prominently reduced after treatment (p<0.05). After treatment, CA19-9 and TSGF levels were remarkably lower in Apatinib group than those in S-1 group (p=0.008, p=0.023), and there was no statistically significant difference in the CEA level between the two groups (p=0.057). After treatment, the quality of life of patients was improved notably in Apatinib group compared with that in S-1 group (p=0.002). Adverse reactions mainly involved hematological toxicity, nausea and vomiting, abnormal renal function, impairment of hepatic function, neurotoxicity, hypertension and hand-foot syndrome, most of which were in grade I-II and relieved after symptomatic treatment and could be tolerated for continued treatment. Serious adverse reactions in grade III-IV occurred rarely. No statistically significant difference was found in the incidence rate of adverse reactions between the two groups of patients (p>0.05). Besides, according to the follow-up results, median overall survival (OS) was 8.1 months vs. 10.7 months and median progression-free survival (PFS) was 4.2 months vs. 5.3 months, respectively, in S-1 group and Apatinib group. The results of log-rank test demonstrated that Apatinib group was superior to S-1 group with respect to OS, showing a statistically significant difference (p=0.028), and no statistically significant difference was found in PFS between the two groups of patients (p=0.159).
CONCLUSION
In the second-line treatment of advanced gastric cancer, apatinib combined with S-1 is superior to S-1 alone in term of clinical efficacy, and its adverse reactions can be tolerated. Apatinib combined with S-1 can prominently improve the quality of life, reduce the serum tumor marker levels and prolong the OS of patients, but it cannot extend the PFS.
Topics: Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Pyridines; Retrospective Studies; Stomach Neoplasms; Tegafur; Treatment Outcome
PubMed: 34268954
DOI: No ID Found -
Scientific Reports Jun 2020Although hyperuricemia has been shown to be associated with the progression of cardiovascular disorder and chronic kidney disease (CKD), there is conflicting evidence as...
Although hyperuricemia has been shown to be associated with the progression of cardiovascular disorder and chronic kidney disease (CKD), there is conflicting evidence as to whether xanthine oxidase (XO) inhibitors confer organ protection besides lowering serum urate levels. In this study, we addressed the cardio-renal effects of XO inhibition in rodent CKD model with hyperuricemia. Sprague-Dawley rats underwent 5/6 nephrectomy and received a uricase inhibitor oxonic acid for 8 weeks (RK + HUA rats). In some rats, a XO inhibitor febuxostat was administered orally. Compared with control group, RK + HUA group showed a significant increase in albuminuria and renal injury. Febuxostat reduced serum uric acid as well as urinary albumin levels. Histological and immunohistochemical analysis of the kidney revealed that febuxostat alleviated glomerular, tubulointerstitial, and arteriolar injury in RK + HUA rats. Moreover, in the heart, RK + HUA showed individual myofiber hypertrophy and cardiac fibrosis, which was significantly attenuated by febuxostat. We found that renal injury and the indices of cardiac changes were well correlated, confirming the cardio-renal interaction in this model. Finally, NF-E2-related factor 2 (Nrf2) and the downstream target heme oxygenase-1 (HO-1) protein levels were increased both in the heart and in the kidney in RK + HUA rats, and these changes were alleviated by febuxostat, suggesting that tissue oxidative stress burden was attenuated by the treatment. These data demonstrate that febuxostat protects against cardiac and renal injury in RK + HUA rats, and underscore the pathological importance of XO in the cardio-renal interaction.
Topics: Animals; Cardiotonic Agents; Disease Models, Animal; Febuxostat; Heart; Hyperuricemia; Kidney Diseases; Kidney Function Tests; Male; Myocardium; Nephrectomy; Oxidative Stress; Oxonic Acid; Protective Agents; Rats, Sprague-Dawley; Xanthine Oxidase
PubMed: 32518351
DOI: 10.1038/s41598-020-65706-6 -
The Oncologist Oct 2021Because S-1 is orally administered, OX-IRIS does not necessitate the continuous infusion of 5-FU and is more convenient. The recommended dose of OX-IRIS was determined...
LESSONS LEARNED
Because S-1 is orally administered, OX-IRIS does not necessitate the continuous infusion of 5-FU and is more convenient. The recommended dose of OX-IRIS was determined to be level -1 (oxaliplatin, 65 mg/m ; irinotecan, 100 mg/m ; S-1, 80 mg/m ), which has manageable safety and promising anticancer activities.
BACKGROUND
OX-IRIS is a new combination therapy of oxaliplatin, irinotecan, and S-1 for unresectable pancreatic ductal adenocarcinoma (PDAC), which may be beneficial because S-1 is administered orally and continuous infusion of 5-fluorouracil (5-FU) is not needed.
METHODS
Patients who had not received prior therapy for unresectable PDAC were enrolled. Adenocarcinoma or adenosquamous histology was required. Oxaliplatin and irinotecan were administered on days 1 and 15; S-1 was administered orally twice a day on days 1-14, followed by 14 days of rest (one cycle). Primary endpoints were dose-limiting toxicity (DLT) and maximum tolerated dose (MTD). Secondary endpoints were safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS).
RESULTS
In level 0 (oxaliplatin, 85 mg/m ; irinotecan, 100 mg/m ; S-1, 80 mg/m ), two of five patients experienced DLT. In level -1 (oxaliplatin, 65 mg/m ; irinotecan, 100 mg/m ; S-1, 80 mg/m ), DLT could not be evaluated in two of eight patients because one cycle was not completed; one of the remaining six patients experienced DLT. Anemia, thrombocytopenia, fatigue, nausea, anorexia, diarrhea, and peripheral sensory neuropathy were seen frequently in levels 0 and -1. ORR was 30% in levels 0 and -1. Median progression-free survival and median overall survival were 4.1 months (95% confidence interval [CI], 0.0-8.9 months) and 13.7 months (95% CI, 4.8-22.6 months), respectively.
CONCLUSION
MTD of OX-IRIS therapy was estimated to be level 0, and the recommended dose (RD) for future trial was level -1.
Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Fluorouracil; Humans; Irinotecan; Oxaliplatin; Oxonic Acid; Pancreatic Neoplasms; Tegafur
PubMed: 34050586
DOI: 10.1002/onco.13838 -
BMC Cancer May 2021The study aimed to investigate the potential benefit of more than 4 courses of S1 adjuvant chemotherapy for patients with pancreatic ductal adenocarcinoma (PDAC) after... (Comparative Study)
Comparative Study
PURPOSE
The study aimed to investigate the potential benefit of more than 4 courses of S1 adjuvant chemotherapy for patients with pancreatic ductal adenocarcinoma (PDAC) after surgery.
METHOD
Data were retrospectively collected from consecutive patients who underwent S-1 adjuvant chemotherapy following curative pancreatectomy between January 2016 and December 2018. Four-courses and > 4 courses cohorts were compared for overall survival (OS) as a primary outcome, and relapse-free survival (RFS) and adverse event incidence as secondary outcomes.
RESULTS
Four-courses and > 4 courses cohorts comprised 99 patients and 64 ones, respectively. TNM stage (stage II vs. I: HR, 2.125; 95% CI, 1.164-4.213; P = 0.015), duration of S-1 administration (4 vs. > 4 courses: HR, 3.113; 95% CI, 1.531-6.327; P = 0.002) and tumor grade (G3 vs. G1/2: HR, 3.887; 95% CI, 1.922-7.861; P < 0.001) were independent prognostic factors. Under the condition of patients' survival time beyond 8 months, the OS of patients in > 4 courses cohort was significantly prolonged compared with that of 4 courses cohort (4 vs. > 4 courses: HR, 2.284; 95% CI, 1.197-4.358; P = 0.012), especially for patients in TNM stageII (4 vs. > 4 courses: HR, 2.906; 95% CI, 1.275-6.623; P = 0.011).RFS and adverse events incidence did not signifcantly difer between both cohorts.
CONCLUSION
Prolonged duration of S-1 intake is beneficial to prognosis of patients with PDAC resection.
Topics: Administration, Oral; Adult; Aged; Antimetabolites, Antineoplastic; Carcinoma, Pancreatic Ductal; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Pancreas; Pancreatectomy; Pancreatic Neoplasms; Prognosis; Retrospective Studies; Tegafur; Time Factors; Young Adult
PubMed: 34034684
DOI: 10.1186/s12885-021-08380-9 -
Cancer Control : Journal of the Moffitt... 2020Small-cell lung cancer (SCLC) is a recalcitrant cancer for its dismal prognosis although extensive research had been done. Four to 6 cycles platinum-based chemotherapy... (Randomized Controlled Trial)
Randomized Controlled Trial
Small-cell lung cancer (SCLC) is a recalcitrant cancer for its dismal prognosis although extensive research had been done. Four to 6 cycles platinum-based chemotherapy is the mainstay treatment for the extensive-stage disease; but the role of maintenance treatment is not fully understood. This is a phase 2, open-label study. Patients with extensive-stage SCLC reaching an objective response or stable disease (SD) after induction chemotherapy were randomly assigned (1:1) with a minimization procedure. One group received oral S-1 and the other group received placebo as maintenance treatment until disease progression or unacceptable toxicities. The primary end point of this study was progression-free survival (PFS), and the secondary end points were overall survival (OS), response rates, and toxicities. This study was based on earlier work, the preliminary results was reported on 2019 ASCO annual meeting. A total of 89 patients were enrolled, of whom 45 received S-1 maintenance therapy and 44 received placebo. The median PFS and OS were 6.35 months and 10.82 months in the S-1 group, as compared to 5.98 months and 10.09 months in the placebo group. The PFS was 7.2 months and 5.3 months, and OS was 12.9 months and 10.9 months in patients with an objective response compared to in patients with SD after induction chemotherapy, respectively. S-1 maintenance therapy did not prolong PFS or OS in patients with extensive-stage SCLC; tumor regression rate was the prognostic factor of PFS or OS. Further research with novel agents in the maintenance setting is warranted.
Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Etoposide; Female; Humans; Irinotecan; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Patient Safety; Small Cell Lung Carcinoma; Survival Rate; Tegafur; Treatment Outcome
PubMed: 32551853
DOI: 10.1177/1073274820932004 -
The Oncologist Aug 2019In terms of efficacy and safety, good results were obtained with S-1 and paclitaxel (PTX) combination therapy.The findings suggest that S-1 and PTX combination therapy...
LESSONS LEARNED
In terms of efficacy and safety, good results were obtained with S-1 and paclitaxel (PTX) combination therapy.The findings suggest that S-1 and PTX combination therapy is a feasible treatment option in patients with previously treated non-small cell lung cancer.
BACKGROUND
Although monotherapy with cytotoxic agents, including docetaxel and pemetrexed, is recommended for patients with previously treated advanced non-small cell lung cancer (NSCLC), its outcomes are unsatisfactory. S-1 is an oral fluoropyrimidine agent that consists of tegafur, 5- chloro-2, 4-dihydroxypyridine, and potassium oxonate. S-1 is approved for patients with gastric cancer in 7 Asian countries and 15 European countries. It is also approved for patients with eight type of cancers, including NSCLC, in Japan. We evaluated the efficacy and toxicity of S-1 and paclitaxel (PTX) combination therapy in patients with previously treated NSCLC.
METHODS
Oral S-1 was administered thrice weekly on days 1-14 at 80, 100, and 120 mg/day in patients with body surface areas of <1.25, 1.25-1.5, and >1.5 m, respectively. PTX was administered at 80 mg/m on days 1 and 8. Primary endpoint was response rate, and secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety.
RESULTS
Forty patients were enrolled, with response and disease control rates of 27.5% and 75.0%, respectively (Fig. 1). Median PFS and OS were 6.5 and 20.7 months, respectively. Grade 3/4 anemia and thrombocytopenia were seen in five (12%) and one (2%) patients, respectively. Febrile neutropenia occurred in three patients (7%). Common grade 3/4 nonhematological toxicities were stomatitis (5% of patients), diarrhea (7% of patients), and interstitial lung disease (one patient). No treatment-related deaths were observed.
CONCLUSION
This S-1 and PTX cotherapy dose and schedule showed satisfactory efficacy, with mild toxicities, in patients with previously treated advanced NSCLC.
Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemotherapy-Induced Febrile Neutropenia; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Paclitaxel; Progression-Free Survival; Tegafur; Thrombocytopenia
PubMed: 31040252
DOI: 10.1634/theoncologist.2019-0290 -
Japanese Journal of Clinical Oncology Mar 2021A multi-institutional phase II study was conducted to evaluate the efficacy and safety of preoperative docetaxel, cisplatin and S-1 therapy in marginally resectable...
BACKGROUND
A multi-institutional phase II study was conducted to evaluate the efficacy and safety of preoperative docetaxel, cisplatin and S-1 therapy in marginally resectable advanced gastric cancer.
METHODS
Patients with macroscopic type 4, large macroscopic type 3 and bulky lymph node metastasis received two cycles of preoperative docetaxel, cisplatin and S-1 therapy (docetaxel 40 mg/m2 and cisplatin 60 mg/m2 on day 1, and S-1 80 mg/m2 for 14 days, every 4 weeks). The primary endpoint was the pathological response rate, with an expected value of 65%.
RESULTS
Thirty-one patients were enrolled in this study. The pathological response rate was 54.8%, and it was higher than the threshold value but lower than the expected rate. The R0 resection rate was 93.5%. The frequencies of grade 3-4 toxicities during docetaxel, cisplatin and S-1 therapy were 41.9% for neutropenia, 6.5% for febrile neutropenia and 32.3% for nausea/vomiting. Grade 2 and 3 surgical morbidities occurred in 23.3 and 6.7% of the patients, respectively.
CONCLUSIONS
Preoperative docetaxel, cisplatin and S-1 therapy was feasible in terms of chemotherapy-related toxicities and surgical morbidity, but the effect did not achieve the expected value. The association between the pathological response rate and survival will be evaluated in the final analysis of this clinical trial.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Postoperative Complications; Preoperative Care; Stomach Neoplasms; Tegafur; Time Factors
PubMed: 33283236
DOI: 10.1093/jjco/hyaa221