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Background: Testicular germ cell tumours (TGCTs) are the most common malignancy in men aged 15–40 years, with increasing incidence worldwide. About 33 ~ 50% of the patients present with metastatic disease at diagnosis. TGCT survivors experience short- and long-term sequelae, including cancer-related fatigue (CRF). Physical activity (PA) has established effects on reducing CRF and other sequelae and improving health-related quality of life (HRQoL). However, its impact on TGCT survivors has so far received little attention. The gut microbiota plays a crucial role in various physiological functions, including cognition and metabolism, and may mediate the effects of PA on CRF and other sequelae, but this has not been investigated in randomized controlled trials. Methods: This national, multicentre, phase-III trial will evaluate the impact of a one-year supervised PA program on CRF and other short- and long-term sequelae in metastatic TGCT patients receiving cisplatin-based chemotherapy combined with etoposide+/-bleomycin. It will also investigate potential mediating effects of the gut microbiota and its metabolites involved in the gut-brain axis on the relationship between PA and CRF and other sequelae. A total of 236 men ≥ 18 years of age with metastatic TGCT (seminoma and non-seminoma) will be enrolled before starting first-line chemotherapy in several French hospitals. The primary (CRF) and secondary (cognitive/psychological/metabolic sequelae, HRQoL, etc.) outcomes and gut microbiota and relevant metabolites will be assessed at inclusion, during and at the end of the one-year intervention, and annually until 10 years since inclusion to assess long-term sequelae, more specifically CRF, cardiovascular toxicities, and second primary cancer occurrence in this population. Discussion: This trial will provide comprehensive and novel insights into the effects of a long-term supervised PA program on CRF and other sequelae in metastatic TGCT patients receiving first-line chemotherapy. It will also contribute to understanding the potential role of the gut microbiota and its metabolites in mediating the effects of PA on these outcomes. The findings of this study will help the development of effective PA interventions to improve the health of TGCT survivors and may have implications for other cancer populations as well. Trial registration: The study was registered on ClinicalTrials.gov (NCT05588700) on 20 Oct. 2022. [ABSTRACT FROM AUTHOR]

Background: Detecting a health-promoting lifestyle in colorectal cancer (CRC) survivors is of paramount importance to manage disease complications, prevent their recurrence, and enhance survival; however, no specialized tool has yet been provided to measure the lifestyle of these patients. Accordingly, this study aimed to develop and determine the psychometric properties of the Health-Promoting Lifestyle Scale in CRC Survivors (HPLS-CRCS). Methods: This study was a mixed study with an exploratory sequential design in two phases. Concept analysis was performed in the first phase according to Schwartz-Barcott and Kim's (2000) hybrid model to explain the concept, identify dimensions, and generate items. In the second phase, psychometrics including validity (face, content, and construct) and reliability (internal consistency and stability) were determined. Responsiveness, interpretability, ease of use, item weighting, and scale scoring were also determined. Results: After explaining the concept, an initial scale encompassing 211 items was developed, content and item analyses were conducted, and the items decreased to 89 items after the face validity assessment. For construct validity, confirmatory factor analysis (CFA) was conducted with a sample size of 500 survivors, and convergent validity was performed for the Persian version of the Health-Promoting Lifestyle Profile II (HPLP-II). Accordingly, 80 items were classified into six factors: activity and rest, spiritual growth, health responsibility, nutrition, interpersonal relationships, and psychological management, with RMSEA = 0.055, χ2/df = 2.484, and χ2 = 6816.516. The reliability of the scale was confirmed, Cronbach's alpha was between 0.865 and 0.928, and the intraclass correlation coefficient (ICC), the standard error of measurement (SEM), the minimal important change (MIC), and the smallest detectable change (SDC) were 0.896, 3.36, 13.86, and 19.87, respectively. Conclusion: The HPLS-CRCS consists of 80 items in six dimensions and is a valid and reliable scale for evaluating the health-promoting lifestyle in CRC survivors. Using this scale to evaluate the healthy lifestyle in these survivors can lead healthcare providers to detect deficiencies and plan the lifestyle of CRC survivors during the post-treatment period. [ABSTRACT FROM AUTHOR]

Background: The morbidity of cancer keeps growing worldwide, and among that, the colorectal cancer (CRC) has jumped to third. Existing early screening tests for CRC are limited. The aim of this study was to develop a diagnostic strategy for CRC by plasma metabolomics. Methods: A targeted amino acids metabolomics method was developed to quantify 32 plasma amino acids in 130 CRC patients and 216 healthy volunteers, to identify potential biomarkers for CRC, and an independent sample cohort comprising 116 CRC subjects, 33 precancerosiss patients and 195 healthy volunteers was further used to validate the diagnostic model. Amino acids-related genes were retrieved from Gene Expression Omnibus and Molecular Signatures Database and analyzed. Results: Three were chosen out of the 32 plasma amino acids examined. The tryptophan / sarcosine / glutamic acid -based receiver operating characteristic (ROC) curve showed the area under the curve (AUC) of 0.955 (specificity 83.3% and sensitivity 96.8%) for all participants, and the logistic regression model were used to distinguish between early stage (I and II) of CRC and precancerosiss patients, which showed superiority to the commonly used carcinoembryonic antigen. The GO and KEGG enrichment analysis proved many alterations in amino acids metabolic pathways in tumorigenesis. Conclusion: This altered plasma amino acid profile could effectively distinguish CRC patients from precancerosiss patients and healthy volunteers with high accuracy. Prognostic tests based on the tryptophan/sarcosine/glutamic acid biomarkers in the large population could assess the clinical significance of CRC early detection and intervention.Highlights: The targeted amino acids metabolomics was applied to profile the alterations of amino acids in colorectal cancer. Plasma amino acids profile shows capability of differentiating the colorectal cancer from the precancerosiss patients and healthy volunteers A diagnostic model Y = 0.001×Trp +0.029×Sar-0.002×Glu-9.427 (unit: ng/mL) was developed and validated for colorectal cancer diagnosis. Amino acids-related differentially expressed genes analysis supported the alterations of amino acids metabolic profile in tumorigenesis. [ABSTRACT FROM AUTHOR]

Background: Studies on the relationship between diet and colorectal cancer (CRC) risk using single food or nutrient approach are widely conducted as opposed to dietary pattern approach. Therefore, this study aimed to determine the major dietary patterns and their association with CRC risk among Malaysians. Methods: Patients aged between 18 and 80 years old from two teaching hospitals in Peninsular Malaysia were recruited through purposive sampling. Socio-demographic information and anthropometry data were assessed before the colonoscopy procedure, and dietary intake was also recorded using a validated semi-quantitative food frequency questionnaire (FFQ). Cases were those patients having histopathologically proven CRC, while controls were those without. Results: Four major dietary patterns were identified: the allergenic diet, plant-based diet, processed diet, and energy-dense diet pattern. After adjusting for potential covariates, the processed diet pattern was consistently associated with CRC (OR = 3.45; 95% CI = 1.25–9.52; P = 0.017) while the plant-based diet, energy-dense diet, and allergenic diet were not associated with CRC risk. Conclusions: The processed diet pattern attributed to a diet high in confectionaries and fast foods was associated with an increased risk of CRC in the Malaysian population. In order to give prevention measures through lifestyle change, more research could be done on the effect of food patterns on faecal microbiota associated with CRC. [ABSTRACT FROM AUTHOR]

Purpose: We sought to determine whether adherence to the American Cancer Society (ACS) Nutrition and Physical Activity Guidelines was associated with better bowel function among colon cancer survivors.Methods: This prospective cohort study included patients surgically treated for stage I-IV colon cancer enrolled in the Lifestyle and Outcomes after Gastrointestinal Cancer (LOGIC) study between February 2017 and May 2021. Participants were assigned an ACS score (0-6 points) at enrollment. Stool frequency (SF) was assessed every 6 months using the EORTC QLQ-CR29. Higher SF is an indication of bowel function impairment. ACS score at enrollment was examined in relation to SF at enrollment and over a 3-year period. Secondarily, we examined associations between the ACS score components (body mass index, dietary factors, and physical activity) and SF. Multivariable models were adjusted for demographic and surgical characteristics.Results: A total of 112 people with colon cancer (59% women, mean age 59.5 years) were included. Cross-sectionally, for every point increase in ACS score at enrollment, the odds of having frequent stools at enrollment decreased by 43% (CI 0.42-0.79; p < 0.01). Findings were similar when we examined SF as an ordinal variable and change in SF over a 3-year period. Lower consumption of red/processed meats and consuming a higher number of unique fruits and vegetables were associated with lower SF (better bowel function) at enrollment.Conclusions: Colon cancer survivors who more closely followed the ACS nutrition and physical activity guidelines had lower SF, an indication of better bowel function.Implications For Cancer Survivors: Our findings highlight the value of interventions that support health behavior modification as part of survivorship care for long-term colon cancer survivors. [ABSTRACT FROM AUTHOR]

Cancer (CA) occurs when cells divide out of control. CA cells usually tend to spread from the initial locus to the near and far tissues, the so-called metastasis. The cause of most cancers is unknown to date yet some factors including viruses, ionizing radiations and certain nutritional factors may promote genetic changes leading to malignant tumor growth. There are several treatment options for cancers including surgery, chemotherapy, radiotherapy and immunotherapy. Although most cancers are life threatening, CA treatments carry many side effects for the affected patient including fatigue, anorexia, hair loss, anemia, neuropathy, gastrointestinal problems like diarrhea or constipation, and weight loss mostly due to loss of lean body mass. As many patients under CA treatment are not able to have an adequate dietary intake, using nutritional supplements (NS) may seem a reasonable approach. Nevertheless, there is some evidence suggesting that some NS may promote CA cell growth and poor prognosis. Here, the most recent findings in this field along with our personal experience are discussed and some recommendations are made based on current evidence. [ABSTRACT FROM AUTHOR]

Growing evidence has demonstrated that fatigue and a high-fat diet trigger diarrhea, and intestinal microbiota disorder interact with diarrhea. However, the association of intestinal mucosal microbiota with fatigue and high-fat diet trigger diarrhea remains unclear. The specific pathogen-free Kunming male mice were randomly divided into the normal group (MCN), standing group (MSD), lard group (MLD), and standing united lard group (MSLD). Mice in the MSD and MSLD groups stood on the multiple-platform apparatus for four h/d for fourteen consecutive days. From the eighth day, mice in the MLD and MSLD groups were intragastric lard, 0.4 mL/each, twice a day for seven days. Subsequently, we analyzed the characteristics and interaction relationship of intestinal mucosal microbiota, interleukin-6 (IL-6), interleukin-17 (IL-17), malondialdehyde (MDA), superoxide dismutase (SOD), and secretory immunoglobulin A (sIgA). Results showed that mice in the MSLD group had an increased number of bowel movements. Compared with the MCN group, the contents of IL-17, and IL-6 were higher (p > 0.05), and the content of sIgA was lower in the MSLD group (p > 0.05). MDA and SOD increased in MLD and MSLD groups. Thermoactinomyces and Staphyloccus were the characteristic bacteria of the MSLD group. And Staphyloccus were positively correlated with IL-6, IL-17, and SOD. In conclusion, the interactions between Thermoactinomyces, Staphyloccus and intestinal inflammation, and immunity might be involved in fatigue and high-fat diet-induced diarrhea. [ABSTRACT FROM AUTHOR]

Although high body-mass index (BMI) is associated with increased risk of developing colorectal cancer (CRC), many CRC patients lose weight before diagnosis. BMI is often reported close to diagnosis, which may have led to underestimation or even reversal of direction of the BMI-CRC association. We aimed to assess if and to what extent potential bias from prediagnostic weight loss has been considered in available epidemiological evidence. We searched PubMed and Web of Science until May 2022 for systematic reviews and meta-analyses investigating the BMI-CRC association. Information on design aspects and results was extracted, including if and how the reviews handled prediagnostic weight loss as a potential source of bias. Additionally, we analyzed how individual cohort studies included in the latest systematic review handled the issue. Overall, 18 reviews were identified. None of them thoroughly considered or discussed prediagnostic weight loss as a potential source of bias. The majority (15/21) of cohorts included in the latest review did not exclude any initial years of follow-up from their main analysis. Although the majority of studies reported having conducted sensitivity analyses in which initial years of follow-up were excluded, results were reported very heterogeneously and mostly for additional exclusions of 1–2 years only. Where explicitly reported, effect estimates mostly increased with increasing length of exclusion. The impact of overweight and obesity on CRC risk may be larger than suggested by the existing epidemiological evidence. [ABSTRACT FROM AUTHOR]

Background: Obesity is a major health concern for breast cancer survivors, being associated with high recurrence and reduced efficacy during cancer treatment. Metformin treatment is associated with reduced breast cancer incidence, recurrence and mortality. To better understand the underlying mechanisms through which metformin may reduce recurrence, we aimed to conduct metabolic profiling of overweight/obese breast cancer survivors before and after metformin treatment. Methods: Fasting plasma samples from 373 overweight or obese breast cancer survivors randomly assigned to metformin (n = 194) or placebo (n = 179) administration were collected at baseline, after 6 months (Reach For Health trial), and after 12 months (MetBreCS trial). Archival samples were concurrently analyzed using three complementary methods: untargeted LC–QTOF-MS metabolomics, targeted LC–MS metabolomics (AbsoluteIDQ p180, Biocrates), and gas chromatography phospholipid fatty acid assay. Multivariable linear regression models and family-wise error correction were used to identify metabolites that significantly changed after metformin treatment. Results: Participants (n = 352) with both baseline and study end point samples available were included in the analysis. After adjusting for confounders such as study center, age, body mass index and false discovery rate, we found that metformin treatment was significantly associated with decreased levels of citrulline, arginine, tyrosine, caffeine, paraxanthine, and theophylline, and increased levels of leucine, isoleucine, proline, 3-methyl-2-oxovalerate, 4-methyl-2-oxovalerate, alanine and indoxyl-sulphate. Long-chain unsaturated phosphatidylcholines (PC ae C36:4, PC ae C38:5, PC ae C36:5 and PC ae C38:6) were significantly decreased with the metformin treatment, as were phospholipid-derived long-chain n-6 fatty acids. The metabolomic profiles of metformin treatment suggest change in specific biochemical pathways known to impair cancer cell growth including activation of CYP1A2, alterations in fatty acid desaturase activity, and altered metabolism of specific amino acids, including impaired branched chain amino acid catabolism. Conclusions: Our results in overweight breast cancer survivors identify new metabolic effects of metformin treatment that may mechanistically contribute to reduced risk of recurrence in this population and reduced obesity-related cancer risk reported in observational studies. Trial registration: ClinicalTrials.gov identifier: NCT01302379 and EudraCT Protocol #: 2015-001001-14. [ABSTRACT FROM AUTHOR]

Currently colorectal cancer (CRC) is the third most prevalent cancer worldwide. Body mass index (BMI) is frequently used in CRC screening and risk assessment to quantitatively evaluate weight. However, the impact of BMI on clinical strategies for CRC has received little attention. Within the framework of the predictive, preventive, and personalized medicine (3PM/PPPM), we hypothesized that BMI stratification would affect the primary, secondary, and tertiary care options for CRC and we conducted a critical evidence-based review. BMI dynamically influences CRC outcomes, which helps avoiding adverse treatment effects. The outcome of surgical and radiation treatment is adversely affected by overweight (BMI ≥ 30) or underweight (BMI < 20). A number of interventions, such as enhanced recovery after surgery and robotic surgery, can be applied to CRC at all levels of BMI. BMI-controlling modalities such as exercise, diet control, nutritional therapy, and medications may be potentially beneficial for patients with CRC. Patients with overweight are advised to lose weight through diet, medication, and physical activity while patients suffering of underweight require more focus on nutrition. BMI assists patients with CRC in better managing their weight, which decreases the incidence of adverse prognostic events during treatment. BMI is accessible, noninvasive, and highly predictive of clinical outcomes in CRC. The cost–benefit of the PPPM paradigm in developing countries can be advanced, and the clinical benefit for patients can be improved with the promotion of BMI-based clinical strategy models for CRC. [ABSTRACT FROM AUTHOR]

Purpose: Fatty acid desaturase (FADS) variants associate with fatty acid (FA) and adipose tissue (AT) metabolism and inflammation. Thus, the role of FADS1 variants in the regulation of dietary linoleic acid (LA)-induced effects on AT inflammation was investigated. Methods: Subjects homozygotes for the TT and CC genotypes of the FADS1-rs174550 (TT, n = 25 and CC, n = 28) or -rs174547 (TT, n = 42 and CC, n = 28), were either recruited from the METabolic Syndrome In Men cohort to participate in an intervention with LA-enriched diet (FADSDIET) or from the Kuopio Obesity Surgery (KOBS) study. GC and LC–MS for plasma FA proportions and eicosanoid concentrations and AT gene expression for AT inflammatory score (AT-InSc) was determined. Results: We observed a diet-genotype interaction between LA-enriched diet and AT-InSc in the FADSDIET. In the KOBS study, interleukin (IL)1 beta mRNA expression in AT was increased in subjects with the TT genotype and highest LA proportion. In the FADSDIET, n-6/LA proportions correlated positively with AT-InSc in those with the TT genotype but not with the CC genotype after LA-enriched diet. Specifically, LA- and AA-derived pro-inflammatory eicosanoids related to CYP450/sEH-pathways correlated positively with AT-InSc in those with the TT genotype, whereas in those with the CC genotype, the negative correlations between pro-inflammatory eicosanoids and AT-InSc related to COX/LOX-pathways. Conclusions: LA-enriched diet increases inflammatory AT gene expression in subjects with the TT genotype, while CC genotype could play a protective role against LA-induced AT inflammation. Overall, the FADS1 variant could modify the dietary LA-induced effects on AT inflammation through the differential biosynthesis of AA-derived eicosanoids. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive tract worldwide and is a serious threat to human life and health. CRC occurs and develops in a multi-step, multi-stage, and multi-gene process, in which abnormal gene expression plays an important role. CRC is currently diagnosed via endoscopy combined with tissue biopsy. Compared with tissue biopsy, liquid biopsy technology has received increasingly more attention and applications in the field of molecular detection due to its non-invasive, safe, comprehensive, and real-time dynamic nature. This review article discusses the application and limitations of current liquid biopsy analytes in the diagnosis, treatment, and prognosis of CRC, as well as directions for their future development. [ABSTRACT FROM AUTHOR]

Dysregulation of tryptophan metabolism has been linked to colorectal tumorigenesis; however, epidemiological studies investigating tryptophan metabolites in relation to colorectal cancer risk are limited. We studied associations of plasma tryptophan, serotonin and kynurenine with colon cancer risk in two studies with cancer patients and controls, and in one prospective cohort: ColoCare Study (110 patients/153 controls), the Colorectal Cancer Study of Austria (CORSA; 46 patients/390 controls) and the European Prospective Investigation into Cancer and Nutrition (EPIC; 456 matched case‐control pairs). Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for colon cancer risk. Tryptophan was inversely associated with colon cancer risk in ColoCare (OR per 1‐SD = 0.44; 95% CI, 0.31‐0.64) and EPIC (OR per 1‐SD = 0.86; 95% CI, 0.74‐0.99). Comparing detectable vs nondetectable levels, serotonin was positively associated with colon cancer in CORSA (OR = 6.39; 95% CI, 3.61‐11.3) and EPIC (OR = 2.03; 95% CI, 1.20‐3.40). Kynurenine was inversely associated with colon cancer in ColoCare (OR per 1‐SD = 0.74; 95% CI, 0.55‐0.98), positively associated in CORSA (OR per 1‐SD = 1.79; 95% CI, 1.27‐2.52), while no association was observed in EPIC. The kynurenine‐to‐tryptophan ratio was positively associated with colon cancer in ColoCare (OR per 1‐SD = 1.38; 95% CI, 1.03‐1.84) and CORSA (OR per 1‐SD = 1.44; 95% CI, 1.06‐1.96), but not in EPIC. These results suggest that higher plasma tryptophan may be associated with lower colon cancer risk, while increased serotonin may be associated with a higher risk of colon cancer. The kynurenine‐to‐tryptophan ratio may also reflect altered tryptophan catabolism during colon cancer development. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to determine the association of physical and psychological symptoms with health care utilization in sexual minority and heterosexual colorectal cancer survivors. Methods: Four hundred eighteen colorectal cancer survivors who were in remission an average of 3 years after their diagnosis were surveyed about their non-emergency health care visits during the preceding 3 months. Survivors reported whether they had experienced any of 21 symptoms common among colorectal cancer survivors in the past week. The relation between having had two or more health care visits in the preceding 3 months and symptoms experienced was assessed using logistic regression, controlling for cancer registry, sexual orientation, sex, age, race/ethnicity, income, and comorbidities. Results: Of the survivors, 12% reported no symptoms, while 12% reported six or more symptoms. Sexual minority survivors reported significantly more weight concerns and more health-related and general anxiety as well as worse body image than heterosexual survivors. Frequent worrying about weight and experiencing sore skin around the anal area or stoma were the two symptoms that significantly contributed towards explaining survivors' increased health care utilization. Conclusion: Weight concerns, which are more common among the heaviest survivors, may prompt survivors to seek help from health care providers, which may lead to more frequent visits. On the other hand, some symptoms, despite their prevalence, had no relationship with the frequency of health care visits, raising questions about whether survivors share these concerns with providers. [ABSTRACT FROM AUTHOR]

For the first time (N = 6291), a study was undertaken to estimate associations between the concentratio ns of red blood cell folate (RBCF) and concentration of six perfluoroalkyl acids (PFAAs), namely, perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), perfluorodecanoic acid (PFDA), perfluorononanoic acid (PFNA), and perfluoroundecanoic acid (PFUnDA) for US adults aged ≥20 years by fitting regression models for the data from National Health and Nutrition Examination Survey for 2007–2014. In almost consistent fashion, increasing concentrations of PFAAs were associated with decreasing concentrations of RBCF. For the total population, for a 10% increase in the concentrations of PFOA, PFOS, PFDA, PFHxS, PFNA, and PFUnDA, percent decreases in RBCF concentrations were found to be 0.33%, 0.66%, 0.83%, 0.16%, 0.89%, and 0.43%, respectively. RBCF concentrations of PFAAs were found to be 1104, 1042, 100, and 936 nmol/L across the four quartiles of PFOS; 112, 1068, 1009, and 948 nmol/L across the four quartiles of PFDA; 1125, 1054, 1005, and 967 nmol/L across the four quartiles of PFNA; and 1099, 1094, 989, and 952 nmol/L across the four quartiles of PFUnDA. Perfluorinated carboxylic acids with carbon chain length > 8 decreased concentrations of RBCF to a greater degree than those carbon chain length ≤ 8. Perfluorinated chemicals with a sulfonic group with carbon chain length > 6 decreased concentrations of RBCF to a greater degree than those carbon chain length ≤ 6. The degree to which concentrations of RBCF decrease varied by age, gender, and race/ethnicity. Non-Hispanic blacks as compared to non-Hispanic whites and Hispanics had the lowest decreases in RBCF concentrations. Mechanisms responsible for negative associations between RBCF and PFAA concentrations are not known and will need to be researched further. [ABSTRACT FROM AUTHOR]

Purpose of Review: Weight loss has long been known to be associated with multiple chronic conditions, including heart failure, COPD, depression, and cancer. Recent reports have suggested that unintentional weight loss (UWL) could be leveraged as an early marker of malignancy. Most studies use standardized cutoff values of ≥5% weight loss to define UWL; however, this threshold has not been validated in different body weight classifications (underweight, overweight, etc.). The purpose of this review was to describe the association between a patient's weight category, the severity of UWL prior to cancer diagnosis, cancer stage at diagnosis, and cancer-specific mortality. Recent Findings: Obesity has been identified as a risk factor for many malignancies. Current data are conflicting about whether patients with obesity are more or less likely to experience UWL prior to diagnosis of a malignancy. Similarly, data analyzing the association between baseline BMI and cancer stage at diagnosis or cancer-specific mortality are mixed. UWL has been associated with an increased risk of all-cause mortality, independent of baseline BMI. Unfortunately, reliable body weight measurements are infrequently obtained, decreasing the likelihood that UWL would be detected clinically. Summary: Weight loss, when unintentional, is a serious condition which requires prompt clinical evaluation. Future studies are needed to objectively quantify UWL among patients with varying baseline BMI. [ABSTRACT FROM AUTHOR]

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Copyright of Der Gastroenterologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Colorectal cancer is the second most common cause of cancer‐related death globally, with marked differences in prognosis by disease stage at diagnosis. We studied circulating metabolites in relation to disease stage to improve the understanding of metabolic pathways related to colorectal cancer progression. We investigated plasma concentrations of 130 metabolites among 744 Stages I–IV colorectal cancer patients from ongoing cohort studies. Plasma samples, collected at diagnosis, were analyzed with liquid chromatography‐mass spectrometry using the Biocrates AbsoluteIDQ™ p180 kit. We assessed associations between metabolite concentrations and stage using multinomial and multivariable logistic regression models. Analyses were adjusted for potential confounders as well as multiple testing using false discovery rate (FDR) correction. Patients presented with 23, 28, 39 and 10% of Stages I–IV disease, respectively. Concentrations of sphingomyelin C26:0 were lower in Stage III patients compared to Stage I patients (pFDR < 0.05). Concentrations of sphingomyelin C18:0 and phosphatidylcholine (diacyl) C32:0 were statistically significantly higher, while citrulline, histidine, phosphatidylcholine (diacyl) C34:4, phosphatidylcholine (acyl‐alkyl) C40:1 and lysophosphatidylcholines (acyl) C16:0 and C17:0 concentrations were lower in Stage IV compared to Stage I patients (pFDR < 0.05). Our results suggest that metabolic pathways involving among others citrulline and histidine, implicated previously in colorectal cancer development, may also be linked to colorectal cancer progression. What's new? Metabolomics is a sophisticated method for investigating whether the metabolite profile of a patient's blood, etc., may reflect the pathophysiological state of cancers and other diseases. In the present study, the authors analyzed circulating metabolites, seeking biomarkers related to colorectal cancer progression. Their results at various stages of colorectal cancer suggest that metabolic pathways involving citrulline, histidine, and other molecules that have been previously implicated in colorectal cancer development may also be linked to progression. [ABSTRACT FROM AUTHOR]

Introduction: Signal transduction cascades drive cellular proliferation, apoptosis, immune, and survival pathways. Proteins have emerged as actionable drug targets because they are often dysregulated in cancer, due to underlying genetic mutations, or dysregulated signaling pathways. Cancer drug development relies on proteomic technologies to identify potential biomarkers, mechanisms-of-action, and to identify protein binding hot spots. Areas covered: Brief summaries of proteomic technologies for drug discovery include mass spectrometry, reverse phase protein arrays, chemoproteomics, and fragment based screening. Protein-protein interface mapping is presented as a promising method for peptide therapeutic development. The topic of biosimilar therapeutics is presented as an opportunity to apply proteomic technologies to this new class of cancer drug. Expert opinion: Proteomic technologies are indispensable for drug discovery. A suite of technologies including mass spectrometry, reverse phase protein arrays, and protein-protein interaction mapping provide complimentary information for drug development. These assays have matured into well controlled, robust technologies. Recent regulatory approval of biosimilar therapeutics provides another opportunity to decipher the molecular nuances of their unique mechanisms of action. The ability to identify previously hidden protein hot spots is expanding the gamut of potential drug targets. Proteomic profiling permits lead compound evaluation beyond the one drug, one target paradigm. [ABSTRACT FROM AUTHOR]

Purpose of Review: Cardiovascular disease is the leading cause of death in the United States. Obese patients are at an increased risk of cardiovascular disease and weight loss can attenuate the risk. Cancer is the second leading cause of death and commonly associated with weight loss. This review focuses on the complex interaction between body weight, cardiovascular disease, and a cancer diagnosis. Recent Findings: The cancer-associated mortality rate has steadily decreased over the last decade. Patients are living longer. Therefore, nonmalignant conditions, such as cardiovascular disease, have assumed an increased importance in cancer survivors. Moreover, patients with cancer are at an especially high risk for cardiovascular disease, due to side effects of various treatments and overlapping risk factors for both malignancy and heart disease. In cancers with a high likelihood of survival or cure, cardiovascular screening, risk factor modification, and attentive treatment of cardiovascular problems should be vigilantly pursued. Summary: Like all individuals, patients with cancer should strive to maintain a healthy weight and participate in regular physical activity, with a goal to optimize cardiac health and health span. Weight loss has a cardioprotective effect in cancer survivors without obvious cancer progression. The notion that cardiac health is a low priority for cancer survivors, particularly for patients with a favorable prognosis, is not true. However, in advanced stages of cancer or with highly lethal cancers, weight loss is associated with poor outcomes and nutritional support to optimize nutritional status and maintain body weight should be prioritized. [ABSTRACT FROM AUTHOR]