The colorectal cancer immune paradox revisited.
Ontology highlight
ABSTRACT:
SUBMITTER: Angelova M
PROVIDER: S-EPMC4801462 | biostudies-other | 2016 Feb
REPOSITORIES: biostudies-other
Similar Datasets
Project description:The striking thing about the happiness-income paradox is that over the long-term--usually a period of 10 y or more--happiness does not increase as a country's income rises. Heretofore the evidence for this was limited to developed countries. This article presents evidence that the long term nil relationship between happiness and income holds also for a number of developing countries, the eastern European countries transitioning from socialism to capitalism, and an even wider sample of developed countries than previously studied. It also finds that in the short-term in all three groups of countries, happiness and income go together, i.e., happiness tends to fall in economic contractions and rise in expansions. Recent critiques of the paradox, claiming the time series relationship between happiness and income is positive, are the result either of a statistical artifact or a confusion of the short-term relationship with the long-term one.
| S-EPMC3012515 | biostudies-literature
Project description:If the occurrence of cancer is the result of a random lottery among cells, then body mass, a surrogate for cells number, should predict cancer incidence. Despite some support in humans, this assertion does not hold over the range of different natural animal species where cancer incidence is known. Explaining the so-called 'Peto's paradox' is likely to increase our understanding of how cancer defense mechanisms are shaped by natural selection. Here, we study how body mass may affect the evolutionary dynamics of tumor suppressor gene (TSG) inactivation and oncogene activation in natural animal species. We show that the rate of TSG inactivation should evolve to lower values along a gradient of body mass in a nonlinear manner, having a threshold beyond which benefits to adaptive traits cannot overcome their costs. We also show that oncogenes may be frequently activated within populations of large organisms. We then propose experimental settings that can be employed to identify protection mechanisms against cancer. We finally highlight fundamental species traits that natural selection should favor against carcinogenesis. We conclude on the necessity of comparing genomes between populations of a single species or genomes between species to better understand how evolution has molded protective mechanisms against cancer development and associated mortality.
| S-EPMC3567476 | biostudies-literature
Project description:Many colorectal cancers (CRCs) develop in genetically susceptible individuals most of whom are not carriers of germ line mismatch repair or APC gene mutations and much of the heritable risk of CRC appears to be attributable to the co-inheritance of multiple low-risk variants. The accumulated experience to date in identifying this class of susceptibility allele has highlighted the need to conduct statistically and methodologically rigorous studies and the need for the multi-centre collaboration. This has been the motivation for establishing the COGENT (COlorectal cancer GENeTics) consortium which now includes over 20 research groups in Europe, Australia, the Americas, China and Japan actively working on CRC genetics. Here, we review the rationale for identifying low-penetrance variants for CRC and the current and future challenges for COGENT.
| S-EPMC3269000 | biostudies-literature
Project description:PIK3CA mutations are amongst the most prevalent somatic mutations in cancer and are associated with resistance to first-line treatment along with low survival rates in a variety of malignancies. There is evidence that patients carrying PIK3CA mutations may benefit from treatment with acetylsalicylic acid, commonly known as aspirin, particularly in the setting of colorectal cancer. In this regard, it has been clarified that Class IA Phosphatidylinositol 3-kinases (PI3K), whose catalytic subunit p110α is encoded by the PIK3CA gene, are involved in signal transduction that regulates cell cycle, cell growth, and metabolism and, if disturbed, induces carcinogenic effects. Although PI3K is associated with pro-inflammatory cyclooxygenase-2 (COX-2) expression and signaling, and COX-2 is among the best-studied targets of aspirin, the mechanisms behind this clinically relevant phenomenon are still unclear. Indeed, there is further evidence that the protective, anti-carcinogenic effect of aspirin in this setting may be mediated in a COX-independent manner. However, until now the understanding of aspirin's prostaglandin-independent mode of action is poor. This review will provide an overview of the current literature on this topic and aims to analyze possible mechanisms and targets behind the aspirin sensitivity of PIK3CA-mutated cancers.
| S-EPMC9250486 | biostudies-literature
Project description:Stranded poly-A RNAseq datasets for 66 adult butterflies
| PRJEB31360 | ENA
Project description:Platelets are the primary cellular mediators of hemostasis and this function firmly acquaints them with a variety of inflammatory processes. For example, platelets can act as circulating sentinels by expressing Toll-like receptors (TLR) that bind pathogens and this allows platelets to effectively kill them or present them to cells of the immune system. Furthermore, activated platelets secrete and express many pro- and anti-inflammatory molecules that attract and capture circulating leukocytes and direct them to inflamed tissues. In addition, platelets can directly influence adaptive immune responses via secretion of, for example, CD40 and CD40L molecules. Platelets are also the source of most of the microvesicles in the circulation and these miniscule elements further enhance the platelet's ability to communicate with the immune system. More recently, it has been demonstrated that platelets and their parent cells, the megakaryocytes (MK), can also uptake, process and present both foreign and self-antigens to CD8+ T-cells conferring on them the ability to directly alter adaptive immune responses. This review will highlight several of the non-hemostatic attributes of platelets that clearly and rightfully place them as integral players in immune reactions.
| S-EPMC7501063 | biostudies-literature
Project description:BackgroundDespite existing studies favoring cemented fixation for patients older than 75 years, a trend toward increased use of uncemented fixation has been described in a 2013 study that used arthroplasty registry data from 2006 to 2010. Updated summarized data are needed beyond 2010 to investigate contemporary trends in the usage of uncemented fixation, especially in patients older than 75 years, and to draw attention to a potential continuing conflict between trends in fixation choice and reported revision risk. Thus, healthcare policy and practice can change and surgeons can make better implant fixation choices.Questions/purposes(1) Has the percentage of primary THAs performed with uncemented fixation changed since 2010? (2) Has the percentage of primary THAs performed in patients older than 75 years performed with uncemented fixation changed since 2010? (3) After stratifying by age, which fixation strategy (cemented versus uncemented and hybrid versus uncemented) is associated with the lowest risk of revision?MethodsNational annual reports from hip arthroplasty registers were identified, and data were extracted from registers published in English or a Scandinavian language, with at least 3 years of reported data in the period from 2010 to 2017. These included Australia, Denmark, England-Wales, Finland, the Netherlands, New Zealand, Romania, Norway, Sweden, and Switzerland, which are all countries with high completeness rates. Data regarding rates of revisions (all causes) related to fixation methods and secondary to different age groups, were taken directly from the registers and no re-analysis was done. The risk estimates were presented as either hazard ratios, rate per 100 component years or as Kaplan-Meier estimates of revision. The age groups compared for Denmark were younger than 50, 50-59, 60-69,70-79, and older than 80 years, and for Australia, New Zealand, England-Wales, and Finland, they were younger than 55, 55-64, 65-74, and older than 75 years. No data were pooled across the registers.ResultsThe current use of uncemented fixation in primary THAs varies between 24% (Sweden) and 71% (Denmark). Increasing use of uncemented fixation has been reported in Norway, Denmark, and Sweden, whereas decreasing use of uncemented fixation has been reported in England-Wales, Australia, New Zealand, and Finland. Examining the group of patients older than 75 years, we found that the use of uncemented fixation has been stable in Netherlands, Sweden, New Zealand, and England-Wales. The use of uncemented fixation is still increasing in Denmark and Australia. In Finland, the use of uncemented fixation has decreased (from 43 % to 24 %) from 2010 to 2017. When compared with uncemented fixation, the risk of revision for hips using cemented fixation was lower in patients older than 75 years for all registers surveyed, except for the oldest males in the Finnish register. In this group, no difference was found between cemented and uncemented fixation.ConclusionOur findings should be used in healthcare policy as feedback on current THAs being performed so as to direct surgeons to choose the right implant fixation, especially in patients older than 75 years, thereby reducing revision risk and increasing the long-term survival of primary THAs. It appears that femoral stem fixation may be the most important revision risk factor in older patients, and future studies should examine this perspective.Level of evidenceLevel III, therapeutic study.
| S-EPMC7282602 | biostudies-literature
Project description:While the clinical importance of CD8+ and CD3+ cells in colorectal cancer (CRC) is well established, the impact of other immune cell subsets is less well described. We sought to provide a detailed overview of the immune landscape of CRC in the largest study to date in terms of patient numbers and in situ analyzed immune cell types. Tissue microarrays from 536 patients were stained using multiplexed immunofluorescence panels, and fifteen immune cell subclasses, representing adaptive and innate immunity, were analyzed. Overall, therapy-naïve CRC patients clustered into an 'inflamed' and a 'desert' group. Most T cell subsets and M2 macrophages were enriched in the right colon (p-values 0.046-0.004), while pDC cells were in the rectum (p = 0.008). Elderly patients had higher infiltration of M2 macrophages (p = 0.024). CD8+ cells were linked to improved survival in colon cancer stages I-III (q = 0.014), while CD4+ cells had the strongest impact on overall survival in metastatic CRC (q = 0.031). Finally, we demonstrated repopulation of the immune infiltrate in rectal tumors post radiation, following an initial radiation-induced depletion. This study provides a detailed analysis of the in situ immune landscape of CRC paving the way for better diagnostics and providing hints to better target the immune microenvironment.
| S-EPMC8583221 | biostudies-literature
Project description:Cancer immunotherapies have achieved unprecedented success in clinic, but they remain largely ineffective in some major types of cancer, such as colorectal cancer with microsatellite stability (MSS CRC). It is therefore important to study tumor microenvironment of resistant cancers for developing new intervention strategies. In this study, we identify a metabolic cue that determines the unique immune landscape of MSS CRC. Through secretion of distal cholesterol precursors, which directly activate RORgt, MSS CRC cells can polarize T cells toward Th17 cells that have well-characterized pro-tumor functions in colorectal cancer. Analysis of large human cancer cohorts revealed an asynchronous pattern of the cholesterol biosynthesis in MSS CRC, which is responsible for the abnormal accumulation of distal cholesterol precursors. Inhibiting the cholesterol biosynthesis enzyme Cyp51, by pharmacological or genetic interventions, reduced the levels of intratumoral distal cholesterol precursors and suppressed tumor progression through a Th17-modulation mechanism in preclinical MSS CRC models. Our study therefore reveals a novel mechanism of cancer-immune interaction and an intervention strategy for the difficult-to-treat MSS CRC.
| S-SCDT-10_1038-S44321-023-00015-9 | biostudies-other
Project description:Background: Body composition may partially explain the U-shaped association between body mass index (BMI) and colorectal cancer survival.Methods: Muscle and adiposity at colorectal cancer diagnosis and survival were examined in a retrospective cohort using Kaplan-Meier curves, multivariable Cox regression, and restricted cubic splines in 3,262 early-stage (I-III) male (50%) and female (50%) patients. Sarcopenia was defined using optimal stratification and sex- and BMI-specific cut points. High adiposity was defined as the highest tertile of sex-specific total adipose tissue (TAT). Primary outcomes were overall mortality and colorectal cancer-specific mortality (CRCsM).Results: Slightly over 42% patients were sarcopenic. During 5.8 years of follow-up, 788 deaths occurred, including 433 from colorectal cancer. Sarcopenic patients had a 27% [HR, 1.27; 95% confidence interval (CI), 1.09-1.48] higher risk of overall mortality than those who were not sarcopenic. Females with both low muscle and high adiposity had a 64% higher risk of overall mortality (HR, 1.64; 95% CI, 1.05-2.57) than females with adequate muscle and lower adiposity. The lowest risk of overall mortality was seen in patients with a BMI between 25 and <30 kg/m2, a range associated with the greatest number of patients (58.6%) who were not at increased risk of overall mortality due to either low muscle or high adiposity.Conclusions: Sarcopenia is prevalent among patients with non-metastatic colorectal cancer, and should, along with adiposity be a standard oncological marker.Impact: Our findings suggest a biologic explanation for the obesity paradox in colorectal cancer and refute the notion that the association between overweight and lower mortality is due solely to methodologic biases. Cancer Epidemiol Biomarkers Prev; 26(7); 1008-15. ©2017 AACR.
| S-EPMC5647152 | biostudies-literature