METHODS: This is a retrospective study, which included 93 CML patients and 98 controls. The polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method was used to genotype the FAS and FASL polymorphisms. Data nanlysis was done using SPSS Version 22. The associations of the genotypes with susceptibility risk and IM response in CML patients were assessed by means of logistic regression analysis and deriving odds ratio with 95% CI.
RESULTS: We observed a significant association between FASL-844T>C polymorphism and CML susceptibility risk and IM response. Variant C allele and FASL-844 CC variant genotype carriers had significantly higher risk for CML susceptibility (OR 1.756, CI 1.163-2.652, p=0.007 and OR 2.261, CI 1.013-5.047, p=0.047 respectively). Conversely, the heterozygous genotype FASL-844 TC conferred lower risk for CML susceptibility (OR 0.379, CI 0.176-0.816, p=0.013). The heterozygous and homozygous variant genotypes and variant C alleles were found to confer a lower risk for the development of IM resistance with OR 0.129 (95% CI: 0.034-0.489 p=0.003), OR 0.257 (95% CI: 0.081-0.818, p=0.021), and OR 0.486 (95% CI: 0.262-0.899, p=0.021) respectively. We also found that FAS-670 A>G polymorphism was not associated with CML susceptibility risk or IM response.
CONCLUSION: The genetic polymorphism FASL-844 T>C may contribute to the CML susceptibility risk and also IM treatment response in CML patients. Accodringly, it may be useful as a biomarker for predicting CML susceptibility risk and IM resistance.
AIM: Our objective was to investigate the potential of AOC3 and LRRC17 as biomarkers for fibroblast activation thus predicting their roles in CRC progression.
METHODS: Immunofluorescence (IF) staining of AOC3 and LRRC17 was performed on myofibroblast line (CCD-112CoN), primary fibroblasts from colorectal tumor (CAFs), and adjacent normal tissue (normal fibroblasts-NFs). SW620 (epithelial CRC cell line) was used as a control. Conventional CAF biomarker (alpha-smooth muscle actin - α-SMA) was included in the IF analysis. Fluorescence intensity was compared between groups using ImageJ software. Proliferation and contractility of treated cells were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and collagen gel contraction assays, respectively. Fibroblast contraction under TGF-β1 treatment was compared to those treated with complete medium (addition of 10% serum) and serum free (SF) medium.
RESULTS: Positive AOC3, LRRC17, and α-SMA expression were observed in colonic fibroblasts, more prominent in CAFs, whereas negative staining was found in SW620. Significant downregulation of AOC3, and upregulations in LRRC17 and α-SMA expression was found in TGF-β1-treated fibroblasts compared to SF medium treatment (p-value<0.05). All fibroblasts exhibited higher proliferation in complete medium and under treatment with conditioned medium from SW620 than SF medium. Significant contraction of NFs was recorded in complete medium and TGF-β1 (p-value<0.01).
CONCLUSION: Our results demonstrate AOC3 and LRRC17 as the potential markers of CAF activation which promote CRC progression.
AIMS: We assessed outcomes of a pilot long-term stroke care clinic which combined secondary prevention and rehabilitation at community level.
SETTINGS AND DESIGN: A prospective observational study of stroke patients treated between 2008 and 2010 at a primary care teaching facility.
SUBJECTS AND METHODS: Analysis of patients was done at initial contact and at 1-year post treatment. Clinical outcomes included stroke risk factor(s) control, depression according to Patient Health Questionnaire (PHQ9), and level of independence using Barthel Index (BI).
STATISTICAL ANALYSIS USED: Differences in means between baseline and post treatment were compared using paired t-tests or Wilcoxon-signed rank test. Significance level was set at 0.05.
RESULTS: Ninety-one patients were analyzed. Their mean age was 62.9 [standard deviation (SD) 10.9] years, mean stroke episodes were 1.30 (SD 0.5). The median interval between acute stroke and first contact with the clinic 4.0 (interquartile range 9.0) months. Mean systolic blood pressure decreased by 9.7 mmHg (t = 2.79, P = 0.007), while mean diastolic blood pressure remained unchanged at 80mmHg (z = 1.87, P = 0.06). Neurorehabilitation treatment was given to 84.6% of the patients. Median BI increased from 81 (range: 2-100) to 90.5 (range: 27-100) (Z = 2.34, P = 0.01). Median PHQ9 scores decreased from 4.0 (range: 0-22) to 3.0 (range: 0-19) though the change was not significant (Z= -0.744, P = 0.457).
CONCLUSIONS: Primary care-driven long-term stroke care services yield favorable outcomes for blood pressure control and functional level.