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Early-onset colorectal cancer (EO-CRC) is a public health concern. Starting screening at 45years has been considered, but there is discrepancy in the recommendations. Racial disparities in EO-CRC incidence and survival are reported; however, racial/ethnic differences in EO-CRC features that could inform a racial/ethnic-tailored CRC screening strategy have not been reported. We compared features and survival among Non-Hispanic White (NHW), Non-Hispanic Black (NHB), and Hispanics with EO-CRC.
CRC patients from SEER 1973-2010 database were identified, and EO-CRC was defined as CRC at <50years. Clinical/pathological features and survival were compared between NHW, NHB, and Hispanics. Cancer-specific survival (CSS) predictors were assessed in a multivariable Cox proportional hazard model.
Of 166,416 patients with CRC, 16,545 (9.9%) had EO-CRC. The EO-CRC frequencies in NHB and Hispanics were higher than NHW (12.7% vs. 16.5% vs. 8.7%, p<0.001). EO-CRC in NHB presents more frequently in females, with wel0 years.
Changes in sex hormones during the menstrual cycle and contraceptive vaginal ring (CVR) use influence immunity within the female genital tract, but the magnitude of these effects and their anatomical location are unclear.
In a prospective study, 29 women were assessed at three-time points follicular phase, luteal phase, and one month after initiation of the ethinyl estradiol/etonogestrel CVR (NuvaRing®, Merck). We performed microarrays on endocervical cytobrushes and measured immune mediators in cervicovaginal fluid, adjusting for bacterial vaginosis and the presence of blood. We compared these results to public gene expression data from the fallopian tubes, endometrium, endo- and ectocervix, and vagina.
Immune-related gene expression in the endocervix and immune mediators in cervicovaginal fluid increased during CVR use versus both menstrual phases, and in the follicular versus luteal phase. The antimicrobial protein granulysin was high during CVR use, intermediate in the follicular phase, and nearly ale genital tract.
Circulating tumor DNA (ctDNA) detected before surgery disappears after complete surgical resection of the cancer. Residual ctDNA indicates minimal residual disease (MRD), which is a cause of recurrence. The presence of long-fragment circulating cell-free DNA (cfDNA) or methylated cfDNA also implies the presence of cancer. In this study, we evaluated the prognostic value of cfDNA methylation and long-fragment cfDNA concentration in gastric cancer patients undergoing curative surgery METHODS Ninety-nine gastric cancer patients were included. Peripheral blood samples were collected before and 1 month after surgery. In patients administered chemotherapy, samples were collected before starting chemotherapy. qPCR was performed to detect long- and short-fragment LINE-1. selleck compound A plasma HELP (HpaII tiny fragment Enrichment by Ligation-mediated PCR) assay to determine the concentration of HpaII small fragments was performed using ligation-mediated PCR and HpaII was quantified as the HpaIIMspI ratio to detect methylation levels of cfDNA.
Overall survival (OS) of patients with low methylation levels before starting treatment was significantly worse than that of patients with high methylation levels (P = 0.006). In the 90 patients who underwent curative surgery, recurrence-free survival (RFS) and OS of patients with low methylation levels before surgery were worse than those with high methylation levels (P=0.08 and P = 0.11, respectively). RFS and OS of patients with high concentrations of long-fragment LINE-1 after surgery were significantly worse than those with low concentrations of long-fragment LINE-1 (P = 0.009, P = 0.04).
Pre-surgical low methylation levels of LINE-1 are a negative prognostic factor. Post-surgical high concentrations of long-fragment LINE-1 indicate MRD and a high risk of recurrence.
Pre-surgical low methylation levels of LINE-1 are a negative prognostic factor. Post-surgical high concentrations of long-fragment LINE-1 indicate MRD and a high risk of recurrence.
Non-alcoholic fatty liver (NAFLD) and its more serious form non-alcoholic steatohepatitis increase risk of hepatocellular carcinoma (HCC). Lipid metabolic alterations and its role in HCC development remain unclear. SPARC (Secreted Protein, Acidic and Rich in Cysteine) is involved in lipid metabolism, NAFLD and diabetes, but the effects on hepatic lipid metabolism and HCC development is unknown. The aim of this study was to evaluate the role of SPARC in HCC development in the context of NAFLD.
Primary hepatocyte cultures from knockout (SPARC
) or wild-type (SPARC
) mice, and HepG2 cells were used to assess the effects of free fatty acids on lipid accumulation, expression of lipogenic genes and de novo triglyceride (TG) synthesis. A NAFLD-HCC model was stabilized on SPARC
or SPARC
mice. Correlations among SPARC, lipid metabolism-related gene expression patterns and clinical prognosis were studied using HCC gene expression dataset.
SPARC
mice increases hepatic lipid deposits over time. Hepatocytes from SPARC
mice or inhibition of SPARC by an antisense adenovirus in HepG2 cells resulted in increased TG deposit, expression of lipid-related genes and nuclear translocation of SREBP1c. Human HCC database analysis revealed that SPARC negatively correlated with genes involved in lipid metabolism, and with poor survival. In NAFLD-HCC murine model, the absence of SPARC accelerates HCC development. RNA-seq study revealed that pathways related to lipid metabolism, cellular detoxification and proliferation were upregulated in SPARC
tumour-bearing mice.
The absence of SPARC is associated with an altered hepatic lipid metabolism, and an accelerated NAFLD-related HCC development.
The absence of SPARC is associated with an altered hepatic lipid metabolism, and an accelerated NAFLD-related HCC development.Chronic fatigue and an impairment of general health-related quality of life (HRQoL) are frequently reported by patients with primary sclerosing cholangitis (PSC). Studies on patients with primary biliary cholangitis (PBC) suggest that, unlike pruritus, fatigue may not be ameliorated by liver transplantation (LT). However, there are few data regarding the assessment of fatigue before and after transplantation in PSC. To investigate the effect of LT on fatigue and HRQoL in patients with PSC, 81 patients with PSC (median age 33 years; 69% men) were prospectively enrolled in this study. The PBC-40 and Short Form 36 (SF-36) questionnaires were used for assessment before and twice after LT. A total of 26 patients who received a transplant for PBC were included as controls. The potential impact of the clinical and laboratory parameters was evaluated by univariate and multivariate analyses. Although in addition to other well-being indexes the median fatigue score improved after LT (P less then 0.001), a detailed analysis demonstrated that fatigue persists in one-third of patients.
Here's my website: https://www.selleckchem.com/Bcl-2.html
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