Hildebrandtalbert4410
Aneuploidy has been proposed as a tool to assess progression in patients with Barrett's esophagus (BE), but has heretofore required multiple biopsies. We assessed whether a single esophageal brushing that widely sampled the esophagus could be combined with massively parallel sequencing to characterize aneuploidy and identify patients with disease progression to dysplasia or cancer.
Esophageal brushings were obtained from patients without BE, with non-dysplastic BE (NDBE), low-grade dysplasia (LGD), high-grade dysplasia (HGD), or adenocarcinoma (EAC). To assess aneuploidy, we used RealSeqS, a technique that uses a single primer pair to interrogate ∼350,000 genome-spanning regions and identify specific chromosome arm alterations. A classifier to distinguish NDBE from EAC was trained on results from 79 patients. An independent validation cohort of 268 subjects was used to test the classifier at distinguishing patients at successive phases of BE progression.
Aneuploidy progression was associated with gains of 1q, 12p, and 20q and losses on 9p and 17p. The entire chromosome 8q was often gained in NDBE, whereas focal gain of 8q24 was identified only when there was dysplasia. Among validation subjects, a classifier incorporating these features with a global measure of aneuploidy scored positive in 96% of EAC, 68% of HGD, but only 7% of NDBE.
RealSeqS analysis of esophageal brushings provides a practical and sensitive method to determine aneuploidy in BE patients. It identifies specific chromosome changes that occur early in NDBE and others that occur late and mark progression to dysplasia. The clinical implications of this approach can now be tested in prospective trials.
RealSeqS analysis of esophageal brushings provides a practical and sensitive method to determine aneuploidy in BE patients. It identifies specific chromosome changes that occur early in NDBE and others that occur late and mark progression to dysplasia. The clinical implications of this approach can now be tested in prospective trials.
Long-term follow up of single dose high-dose rate brachytherapy (HDR BT) for localised prostate cancer has revealed higher than expected rates of biochemical and local failure. This study aimed (i) to investigate the pattern of relapse within the prostate with reference to the initial site of disease in those patients; and (ii) to examine if there were any relationships between the HDR BT dosimetric parameters to these areas of recurrence.
A retrospective review of treatment records of patients who received 19Gy single fraction of HDR BT was carried out. A matched pair analysis used one control for each biochemical recurrence case matched with pre-treatment Clinical target volume (CTV) size, Gleason score, T stage, risk category and presence of an identifiable dominant intraprostatic nodule (DIL) for each biochemical recurrence case identified. For all datasets, the pre HDR BT DILs were delineated on the diagnostic pre-treatment T2-weighted MRI and planning CT images. For patients with local recurrence pois. No statistically significant differences were found in all CTV, PTV, DIL and OAR dosimetric parameters between cases and controls (p>0.05). For the Cox regression analysis, none of the covariates investigated were found to be statistically significant factors to predict for bPFS, LC-PFS and DIL-PFS.
No associations between biochemical recurrences and HDR BT dosimetry were identified in our cohort of patients receiving 19Gy single fraction HDR BT. A large proportion of recurrences occurred at the site of original disease. HDR BT for intermediate/high risk prostate cancer should be undertaken using a minimum of two fractions.
No associations between biochemical recurrences and HDR BT dosimetry were identified in our cohort of patients receiving 19 Gy single fraction HDR BT. A large proportion of recurrences occurred at the site of original disease. HDR BT for intermediate/high risk prostate cancer should be undertaken using a minimum of two fractions.Dichapetalum madagascariense Poir (Dichapetalaceae) is traditionally used to treat bacterial infections, jaundice, urethritis and viral hepatitis in Africa. Its root contains a broad spectrum of biologically active dichapetalins. To evaluate the plant's effect on human MCF-7 cells and its' antibacterial and antiparasitic potentials, we isolated and identified the known dichapetalins A and M from the roots. Sulfopin nmr Both dichapetalins were tested on six bacterial strains (Shigella flexneri, Bacillus cereus, Salmonella paratyphi B, Listeria monocytogenes, Escherichia coli, Staphylococcus aureus) and two parasite strains; Trypanosoma brucei brucei, and Leishmania donovani using the Alamar Blue assay system. Dichapetalins A and M were more potent against B. cereus with IC50 values of 11.15 and 3.15 μg/ml, respectively, compared to the positive control ampicillin (IC50 = 19.50 μg/ml). Dichapetalins A (IC50 = 74.22 μg/ml) and M (IC50 = 72.34 μg/ml) were less active against T. b. brucei, compared to the standard Suramin (IC50 = 4.96 μg/ml). Dichapetalin M showed moderate activity against L. donovani (Amphotericin B IC50 = 0.21 μg/ml) with an IC50 of 16.80 μg/ml. In human MCF-7 cells expressing the NR1I2 receptor, the activity of dichapetalin M was higher (IC50 = 4.71 μM and 3.95 μM) for 48 and 72 h of treatment, respectively compared to Curcumin with IC50 of 17.49 μM and 12.53 μM for 48 and 72 h of treatment, respectively. Results from in vitro expression studies with qPCR confirmed an antagonistic effect of dichapetalin M on PXR (NR1I2) signaling; supporting the PXR signaling pathway as a possible mode of action of dichapetalin M as predicted by in silico results. These findings confirm previous studies that D. madagascariense can be a source of potential lead compounds for development of novel antibiotic, antiparasitic and anticancer medicines, and provide further insights into the mechanism of action of the dichapetalins.Despite the popularity of theraphosids, detailed reports on bite symptoms are still limited to few geographic regions and subfamilies. We therefore examined 363 published bite reports and noticed muscles cramps caused by theraphosids from nearly all continents and subfamilies. Symptoms are mostly locally restricted and mild, but 12.7% of victims experience pronounced cramps with highest incidence rates by Poecilotheriinae, Harpactirinae and Stromatopelminae subfamilies. We discuss how variations in venom quantity correlate with muscle cramp prevalence.
