Summary Background & aims Green tea catechins, especially epigallocatechin-3-gallate (EGCG), have been associated with cancer prevention and treatment. This has resulted in an increased number of ...studies evaluating the effects derived from the use of this compound in combination with chemo/radiotherapy. This review aims at compiling latest literature on this subject. Methods Keywords including EGCG, cancer, chemotherapy, radiotherapy and side effects, were searched using PubMed and ScienceDirect databases to identify, analyze, and summarize the research literature on this topic. Most of the studies on this subject up to date are preclinical. Relevance of the findings, impact factor, and date of publication were critical parameters for the studies to be included in the review. Results Additive and synergistic effects of EGCG when combined with conventional cancer therapies have been proposed, and its anti-inflammatory and antioxidant activities have been related to amelioration of cancer therapy side effects. However, antagonistic interactions with certain anticancer drugs might limit its clinical use. Conclusions The use of EGCG could enhance the effect of conventional cancer therapies through additive or synergistic effects as well as through amelioration of deleterious side effects. Further research, especially at the clinical level, is needed to ascertain the potential role of EGCG as adjuvant in cancer therapy.
The review aims at elucidating the role of lipid peroxidation of polyunsaturated fatty acids (PUFAs) in colorectal cancer (CRC) risk and treatment.
CRC is one of the most overriding threats to public ...health. Despite a broad range of treatments, up to 50% of patients will inevitably develop incurable metastatic disease. Peroxidation of PUFAs contributes to augmentation of oxidative stress and causes in consequence inflammation, which is one of the possible carcinogenic factors of CRC. End products of PUFAs might be used as biomarkers for CRC detection and surveillance for treatment. They also have cytotoxic effect in CRC cells. Experimental results suggest that ω-3 PUFAs could increase the efficacy of radiotherapy and chemotherapy of CRC.
Lipid peroxidation, one factor of oxidative stress, might play a paramount role not only in carcinogenesis but also in potential therapeutic strategy on CRC. End products of lipid peroxidation, such as malondialdehyde, 4-hydroxy-2-nonenal, and isoprostanes, could be used as biomarkers for cancer detection, surveillance of treatment outcome and prognostic index for CRC patients. Furthermore, malondialdehyde and 4-hydroxy-2-nonenal have cytotoxic effect not only in normal cells but also in CRC cancer cells, which implies the potential role of PUFAs in CRC treatment.
The advantages of prehabilitation in surgical oncology are unclear. This systematic review aims to (1) evaluate the latest evidence of preoperative prehabilitation interventions on postoperative ...outcomes after gastrointestinal (GI) cancer surgery and (2) discuss new potential therapeutic targets as part of prehabilitation. Randomized controlled trials published between January 2017 and August 2022 were identified through Medline. The population of interest was oncological patients undergoing GI surgery. Trials were considered if they evaluated prehabilitation interventions (nutrition, physical activity, probiotics and symbiotics, fecal microbiota transplantation, and ghrelin receptor agonists), alone or combined, on postoperative outcomes. Out of 1180 records initially identified, 15 studies were retained. Evidence for the benefits of unimodal interventions was limited. Preoperative multimodal programs, including nutrition and physical activity with or without psychological support, showed improvement in postoperative physical performance, muscle strength, and quality of life in patients with esophagogastric and colorectal cancers. However, there was no benefit for postoperative complications, hospital length of stay, hospital readmissions, and mortality. No trial evaluated the impact of fecal microbiota transplantation or oral ghrelin receptor agonists. Further studies are needed to confirm our findings, identify patients who are more likely to benefit from surgical prehabilitation, and harmonize interventions.
SummaryRationaleAccurate evaluation of the energy needs is required to optimize nutrition support of critically ill patients. Recent evaluations of indirect calorimeters revealed significant ...differences among the devices available on the market. A new indirect calorimeter (Q-NRG ®, Cosmed, Roma, Italy) has been developed by a group of investigators supporting the international calorimetry study initiative (ICALIC) to achieve ultimate accuracy for measuring energy expenditure while being easy to use, and affordable. This study aims to validate the precision and the accuracy of the Q-NRG ® in the in-vitro setting, within the clinically relevant range for adults on mechanical ventilation in the ICU. Mass spectrometry is the reference method for the gas composition analysis to evaluate the analytic performances of the Q-NRG ®. MethodsThe accuracy and precision of the O 2 and CO 2 measurements by the Q-NRG were evaluated by comparing the measurements of known O 2 and CO 2 gas mixtures with the measurements by the mass spectrometer (Extrel, USA). The accuracy and precision of the Q-NRG ® for measurements of VO 2 (oxygen consumption) and VCO 2 (CO 2 production) at clinically relevant ranges (150, 250 and 400 ml/min STPD) were evaluated by measuring simulated gas exchange under mechanically ventilated setting at different FiO 2 settings (21–80%), in comparison to the reference measurements by the mass spectrometer-based mixing chamber system. ResultsThe measurements of gas mixtures of predefined O 2 and CO 2 concentrations by the Q-NRG ® were within 2% accuracy versus the mass spectrometer measurements in Passing Bablok regression analysis. In a mechanically ventilated setting of FiO 2 from 21 up to 70%, the Q-NRG ® measurements of simulated VO 2 and VCO 2 were within 5% difference of the reference mass spectrometer measurements. ConclusionIn vitro evaluation confirms that the accuracy of the Q-NRG ® indirect calorimeter is within 5% at oxygen enrichment to 70%; i.e. maximum expected for clinical use. Further recommendations for the clinical use of the Q-NRG ® by will be released once the ongoing multi-center study is completed.
Abstract Objective The anticancer action exerted by polyunsaturated fatty acid peroxidation may not be reproduced by commercially available lipid emulsions rich in vitamin E. Therefore, we evaluated ...the effects of fish oil (FO) emulsion containing α-tocopherol 0.19 g/L on human colorectal adenocarcinoma cells and tumors. Methods HT-29 cell growth, survival, apoptosis, and lipid peroxidation were analyzed after a 24-h incubation with FO 18 to 80 mg/L. Soybean oil (SO) emulsion was used as an isocaloric and isolipidic control. In vivo, nude mice bearing HT-29 tumors were sacrificed 7 d after an 11-d treatment with intravenous injections of FO or SO 0.2 g ∙ kg−1 ∙ d−1 FO or SO to evaluate tumor growth, necrosis, and lipid peroxidation. Results The FO inhibited cell viability and clonogenicity in a dose-dependent manner, whereas SO showed no significant effect compared with untreated controls. Lipid peroxidation and cell apoptosis after treatment with FO 45 mg/L were increased 2.0-fold ( P < 0.01) and 1.6-fold ( P = 0.04), respectively. In vivo, FO treatment did not significantly affect tumor growth. However, immunohistochemical analyses of tumor tissue sections showed a decrease of 0.6-fold ( P < 0.01) in the cell proliferation marker Ki-67 and an increase of 2.3-fold ( P = 0.03) in the necrotic area, whereas malondialdehyde and total peroxides were increased by 1.9-fold ( P = 0.09) and 7.0-fold ( P < 0.01), respectively, in tumors of FO-treated compared with untreated mice. Conclusion These results suggest that FO but not SO has an antitumor effect that can be correlated with lipid peroxidation, despite its vitamin E content.
Indirect calorimetry (IC) is the only way to measure in real time energy expenditure (EE) and to optimize nutrition support in acutely and chronically ill patients. Unfortunately, most of the ...commercially available indirect calorimeters are rather complex to use, expensive and poorly accurate and precise. Therefore, an innovative device (Q-NRG®, COSMED, Rome, Italy) that matches clinicians’ needs has been developed as part of the multicenter ICALIC study supported by the two academic societies ESPEN and ESICM. The aim of this study was to evaluate the accuracy and intra- and inter-unit precision of this new device in canopy dilution mode in vitro and in spontaneously breathing adults.
Accuracy and precision of oxygen consumption (VO2) and carbon dioxide production (VCO2) measurements were evaluated in vitro and in 15 spontaneously breathing healthy adults by interchanging three Q-NRG® units in a random order. In vitro validation was performed by gas exchange simulation using high-precision gas mixture and mass flow controller. Accuracy was calculated as error of measured values against expected ones based on volume of gas infused. Respiratory coefficient (RQ) accuracy was furthermore assessed using the ethanol-burning test. To evaluate the intra- and inter-unit precisions, the coefficient of variation (CV% = SD/Mean*100) was calculated, respectively, from the mean ± SD or the mean ± SD of the three mean values of VO2, VCO2, RQ and EE measured by each Q-NRG® units. In vivo accuracy measurement of the Q-NRG® was assessed by simultaneous comparison with mass spectrometry (MS) gas analysis, using Bland-Altman plot, Pearson correlation and paired t-test (significance level of p = 0.05).
In vitro evaluation of the Q-NRG® accuracy showed measurement errors <1% for VO2, VCO2 and EE and <1.5% for RQ. Evaluation of the intra- and inter-unit precision showed CV% ≤1% for VO2 and EE and CV% ≤1.5% for VCO2 and RQ measurements, except for one Q-NRG® unit where CV% was 2.3% for VO2 and 3% for RQ. Very good inter-unit precision was confirmed in vivo with CV% equal to 2.4%, 3%, 2.8% and 2.3% for VO2, VCCO2, RQ and EE, respectively. Comparison with MS showed correlation of 0.997, 0.987, 0.913 and 0.997 for VO2, VCO2, RQ and EE respectively (p ≤ 0.05). Mean deviation of paired differences was 1.6 ± 1.4% for VO2, -1.5 ± 2.5% for VCO2, -3.1 ± 2.6% for RQ and 0.9 ± 1.4% for EE.
Both in vitro and in vivo measurements of VO2, VCO2, RQ and EE on three Q-NRG® units showed minimal differences compared to expected values and MS and very low intra- and inter-unit variability. These results confirm the very good accuracy and precision of the Q-NRG® indirect calorimeter in canopy dilution mode in spontaneously breathing adults.
It has been shown that long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) could act synergistically with 5-fluorouracil (5-FU) to kill cancer cells. To facilitate their simultaneous transport in ...the bloodstream, we synthesized, for the first time, liposomes (LIPUFU) containing 5-FU in the aqueous core and docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) at a ratio of 1:2 in the lipid bilayer. LIPUFU werestable with uniform size of 154 ± 4 nm, PDI of 0.19 ± 0.03 and zeta potential of -41 ± 2 mV. They contained 557 ± 210 μmol/l DHA, 1467 ± 362 μmol/l EPA, and 9.8 ± 1.1 μmol/l 5-FU. Control liposomes without (LIP) or with only 5-FU (LIFU) or n-3 PUFAs (LIPU) were produced in a similar way. The effects of these different liposomal formulations on the cell cycle, growth, and apoptosis were evaluated in two human colorectal cancer (CRC) cell lines differing in sensitivity to 5-FU, using fluorescence-activated cell sorting analyses. LIPUFU were more cytotoxic than LIP, LIFU, and LIPU in both LS174T (p53
+/+
, bax
−/−
) and HT-29 (p53
−/0
, bax
+/+
) cell lines. Similar to LIFU, LIPUFU increased the percentage of cells in S phase, apoptosis, and/or necrosis. The cytotoxic potential of LIPUFU was confirmed
in vivo
by tumor growth inhibition in the chicken chorioallantoic membrane model. These results suggest that LIPUFU could be considered to facilitate the simultaneous transport of 5-FU and n-3 PUFAs to the tumor site, in particular in case of CRC liver metastases.
Summary Introduction The international ICALIC initiative aims at developing a new indirect calorimeter according to the needs of the clinicians and researchers in the field of clinical nutrition and ...metabolism. The project initially focuses on validating the calorimeter for use in mechanically ventilated acutely ill adult patient. However, standard methods to validate the accuracy of calorimeters have not yet been established. This paper describes the procedures for the in-vitro tests to validate the accuracy of the new indirect calorimeter, and defines the ranges for the parameters to be evaluated in each test to optimize the validation for clinical and research calorimetry measurements. Methods Two in-vitro tests have been defined to validate the accuracy of the gas analyzers and the overall function of the new calorimeter. 1) Gas composition analysis allows validating the accuracy of O2 and CO2 analyzers. Reference gas of known O2 (or CO2 ) concentration is diluted by pure nitrogen gas to achieve predefined O2 (or CO2 ) concentration, to be measured by the indirect calorimeter. O2 and CO2 concentrations to be tested were determined according to their expected ranges of concentrations during calorimetry measurements. 2) Gas exchange simulator analysis validates O2 consumption (VO2 ) and CO2 production (VCO2 ) measurements. CO2 gas injection into artificial breath gas provided by the mechanical ventilator simulates VCO2 . Resulting dilution of O2 concentration in the expiratory air is analyzed by the calorimeter as VO2 . CO2 gas of identical concentration to the fraction of inspired O2 (FiO2 ) is used to simulate identical VO2 and VCO2 . Indirect calorimetry results from publications were analyzed to determine the VO2 and VCO2 values to be tested for the validation. Results O2 concentration in respiratory air is highest at inspiration, and can decrease to 15% during expiration. CO2 concentration can be as high as 5% in expired air. To validate analyzers for measurements of FiO2 up to 70%, ranges of O2 and CO2 concentrations to be tested were defined as 15–70% and 0.5–5.0%, respectively. The mean VO2 in 426 adult mechanically ventilated patients was 270 ml/min, with 2 standard deviation (SD) ranges of 150–391 ml/min. Thus, VO2 and VCO2 to be simulated for the validation were defined as 150, 250, and 400 ml/min. Conclusion The procedures for the in-vitro tests of the new indirect calorimeter and the ranges for the parameters to be evaluated in each test have been defined to optimize the validation of accuracy for clinical and research indirect calorimetry measurements. The combined methods will be used to validate the accuracy of the new indirect calorimeter developed by the ICALIC initiative, and should become the standard method to validate the accuracy of any future indirect calorimeters.