Post‐diagnosis adiposity, physical activity, sedentary behaviour, dietary factors, supplement use and colorectal cancer prognosis: Global Cancer Update Programme ( CUP Global) summary of evidence grading

Based on the World Cancer Research Fund Global Cancer Update Programme, we performed systematic reviews and meta‐analyses to investigate the association of post‐diagnosis adiposity, physical activity, sedentary behaviour, and dietary factors with colorectal cancer prognosis. We searched PubMed and Embase until 28th February, 2022. An independent expert committee and expert panel graded the quality of evidence. A total of 167 unique publications were reviewed, and all but five were observational studies. The quality of the evidence was graded conservatively due to the high risk of several biases. There was evidence of non‐linearity in the associations between body mass index and colorectal cancer prognosis. The associations appeared reverse J‐shaped, and the quality of this evidence was graded as limited (likelihood of causality: limited‐no conclusion). The evidence on recreational physical activity and lower risk of all‐cause mortality (relative risk [RR] highest vs. lowest: 0.69, 95% confidence interval [CI]: 0.62–0.77) and recurrence/disease‐free survival (RR: 0.80, 95% CI: 0.70–0.92) was graded as limited‐suggestive. There was limited‐suggestive evidence for the associations between healthy dietary and/or lifestyle patterns (including diets that comprised plant‐based foods), intake of whole grains and coffee with lower risk of all‐cause mortality, and between unhealthy dietary patterns and intake of sugary drinks with higher risk of all‐cause mortality. The evidence for other exposures on colorectal cancer outcomes was sparse and graded as limited‐no conclusion. Analyses were conducted excluding cancer patients with metastases without substantial changes in the findings. Well‐designed intervention and cohort studies are needed to support the development of lifestyle recommendations for colorectal cancer patients

EVI1 phosphorylation at S436 regulates interactions with CtBP1 and DNMT3A and promotes self-renewal

From Springer Nature via Jisc Publications RouterHistory: received 2020-04-03, rev-recd 2020-08-02, accepted 2020-08-03, collection 2020-10, registration 2020-10-08, pub-electronic 2020-10-20, online 2020-10-20Publication status: PublishedFunder: Bloodwise; doi: https://doi.org/10.13039/501100007903; Grant(s): 10037, 150380, 19007Funder: Cancer Research UK (CRUK); doi: https://doi.org/10.13039/501100000289; Grant(s): C5759/A20971, C18601/A5901Funder: Kay Kendall Leukaemia Fund (KKLF); doi: https://doi.org/10.13039/501100000402; Grant(s): KKL 792Funder: CHILDREN with CANCER UK; doi: https://doi.org/10.13039/501100001273; Grant(s): 201609Funder: Kuweit Ministry of EducationFunder: Deutsche Forschungsgemeinschaft (German Research Foundation); doi: https://doi.org/10.13039/501100001659; Grant(s): EXC 62/1Abstract: The transcriptional regulator EVI1 has an essential role in early development and haematopoiesis. However, acute myeloid leukaemia (AML) driven by aberrantly high EVI1 expression has very poor prognosis. To investigate the effects of post-translational modifications on EVI1 function, we carried out a mass spectrometry (MS) analysis of EVI1 in AML and detected dynamic phosphorylation at serine 436 (S436). Wild-type EVI1 (EVI1-WT) with S436 available for phosphorylation, but not non-phosphorylatable EVI1-S436A, conferred haematopoietic progenitor cell self-renewal and was associated with significantly higher organised transcriptional patterns. In silico modelling of EVI1-S436 phosphorylation showed reduced affinity to CtBP1, and CtBP1 showed reduced interaction with EVI1-WT compared with EVI1-S436A. The motif harbouring S436 is a target of CDK2 and CDK3 kinases, which interacted with EVI1-WT. The methyltransferase DNMT3A bound preferentially to EVI1-WT compared with EVI1-S436A, and a hypomethylated cell population associated by EVI1-WT expression in murine haematopoietic progenitors is not maintained with EVI1-S436A. These data point to EVI1-S436 phosphorylation directing functional protein interactions for haematopoietic self-renewal. Targeting EVI1-S436 phosphorylation may be of therapeutic benefit when treating EVI1-driven leukaemia

Post-diagnosis adiposity, physical activity, sedentary behaviour, dietary factors, supplement use and colorectal cancer prognosis: Global Cancer Update Programme (CUP Global) summary of evidence grading

Based on the World Cancer Research Fund Global Cancer Update Programme, we performed systematic reviews and meta-analyses to investigate the association of post-diagnosis adiposity, physical activity, sedentary behaviour, and dietary factors with colorectal cancer prognosis. We searched PubMed and Embase until 28th February, 2022. An independent expert committee and expert panel graded the quality of evidence. A total of 167 unique publications were reviewed, and all but five were observational studies. The quality of the evidence was graded conservatively due to the high risk of several biases. There was evidence of non-linearity in the associations between body mass index and colorectal cancer prognosis. The associations appeared reverse J-shaped, and the quality of this evidence was graded as limited (likelihood of causality: limited-no conclusion). The evidence on recreational physical activity and lower risk of all-cause mortality (relative risk [RR] highest vs. lowest: 0.69, 95% confidence interval [CI]: 0.62-0.77) and recurrence/disease-free survival (RR: 0.80, 95% CI: 0.70-0.92) was graded as limited-suggestive. There was limited-suggestive evidence for the associations between healthy dietary and/or lifestyle patterns (including diets that comprised plant-based foods), intake of whole grains and coffee with lower risk of all-cause mortality, and between unhealthy dietary patterns and intake of sugary drinks with higher risk of all-cause mortality. The evidence for other exposures on colorectal cancer outcomes was sparse and graded as limited-no conclusion. Analyses were conducted excluding cancer patients with metastases without substantial changes in the findings. Well-designed intervention and cohort studies are needed to support the development of lifestyle recommendations for colorectal cancer patients

Measurement of the intact sulfate and glucuronide conjugates of phytoestrogens in human urine using direct injection HPLC and electrospray tandem mass spectrometry with [¹³C₃]isoflavone internal standards

A method has been developed for the analysis of phytoestrogens and their conjugates in human urine using liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Stable isotopically labeled [C-13(3)]daidzein and [C-13(3)]genistein were synthesized and used as internal standards for isotope dilution mass spectrometry, Free aglycons and intact glucuronide, sulfate, diglucuronide, disulfate, and mixed sulfoglucuronide conjugates of isoflavones and lignans were, observed in naturally incurred urine samples. Sample pretreatment was not necessary, other than addition of internal standards and pH adjustment. Urine was injected directly onto the analytical column. The limits of detection were generally &lt;50 ng/ml. precision was generally &lt;10% CV for conjugates. Total hydrolyzed daidzein and genistein were measured against quality assurance urine sample and were accurate to within 12%. The accuracy of conjugate measurement can not be ascertained, as no reference samples are available. The mean sum of daidzein and its conjugates was within 20% of the hydrolyzed value. Concentrations of the free aglycons of up to 22% of genistein and 18% of daidzein were observed. The average pattern was ca. 54% 7-glucuronide, 25% 4'-glucuronide, 13% monosulfates, 7% free daidzein, 0.9% sulfoglucuronides, 0.4% diglucuronide, and &lt;0.1% disulfate. Selective enzymatic de-conjugation with glucuronidase and mixed glucuronidase/sulfatase were used to validate the accuracy of the quantitation of the intact daidzein conjugates. There were no apparent sex differences, or conditioning effects on the conjugation profile of isoflavones after chronic dosing. (C) 2002 Elsevier Science (USA). All rights reserved.</p