926 research outputs found
Peptide Biomarkers for Identifying the Species Origin of Gelatin Using Coupled UPLC-MS/MS
Liquid chromatography linked with mass spectrometry (LC–MS/MS) was used to analyse gelatin from four different species after a trypsin digest. Using chemometric software to analyse the data it was possible to find peptide fragments that were specific to each species of gelatin: porcine, bovine, chicken or fish. Identification of these peptides was challenging due to the destructive nature of gelatin manufacture. The untargeted workflow method developed allowed identification of 21 unknown gelatin samples with 100% accuracy. Fish gelatin is made from a large range of different species that do not share a common differentiating protein but it was shown that the protein from a parasitic bacteria could be used to identify fish gelatin.</p
Human pluripotent stem cells as tools for high-throughput and high-content screening in drug discovery
A significant bottleneck in drug discovery is the lack of suitable models for sensitive, reliable, and rapid assessment of lead molecules in preclinical stages of drug discovery. Human pluripotent stem cells (hPSCs) derived either from early human blastocysts (human embryonic stem cells) or by reprogramming somatic cells to a pluripotent state (human-induced pluripotent stem cells) can be propagated extensively in vitro while retaining the ability to differentiate into any specialized cell type within the body. In this review, we discuss how these unique features of hPSCs could offer a way of producing relevant in vitro models amenable to high-throughput testing for drug discovery. We summarize recent progress in inducing differentiation of hPSCs to specific cell types, and describe the ongoing efforts in applying hPSCs and their differentiated derivatives in disease modeling, drug discovery, and developmental toxicology. Moreover, we review the applications of high-content imaging assays in detecting the changes in the phenotype of hPSCs and their differentiated progeny. Finally, we highlight challenges that need to be overcome in order for the application of hPSC technology to fully benefit drug discovery
A randomised trial comparing combination chemotherapy using mitomycin C, mitozantrone and methotrexate (3M) with vincristine, anthracycline and cyclophosphamide (VAC) in advanced breast cancer.
This paper describes a randomised clinical trial in patients with advanced breast cancer, comparing the regimen 3M, mitomycin C 7-8 mg m-2 (day 1), mitozantrone 7-8 mg m-2 (day 1 and 21), methotrexate 35 mg m-2 (day 1 and 21) given on a 42 day cycle with a standard anthracycline containing regimen, VAC, vincristine 1.4 mg m-2 (day 1), anthracycline (adriamycin or epirubicin) 30 mg m-2 (day 1), cyclophosphamide 400 mg m-2 (day 1) given on a 21 day cycle. Of a total of 217 patients, 107 were randomised to 3M and 110 to VAC and a mean of 5.5 courses was given per patient. The overall response rate (complete and partial) was 53% (95% Confidence Limits (CL): 43-62%) for 3M and 49% (CL; 39-58%) for VAC. The response according to sites of metastases was the same for both treatment groups. Symptomatic toxicity including alopecia, neuropathy, vomiting (P less than 0.001) and nausea (P less than 0.01) were significantly less for 3M. Myelosuppression including leucopenia (P less than 0.001) and thrombocytopenia (P less than 0.001) was significantly greater with 3M at day 21, although there was no difference in nadir counts in patients at special risk of myelosuppression and there was no evidence of an increase in infective or bleeding complications. There was no significant difference in the duration of response to 3M (10 months, CL 6-15) and VAC (11 months, CL 7-12), nor in survival (3M, 8 months, CL 6-12; VAC, 10 months, CL 8-12). These results indicate that 3M is as effective as, but has significantly less symptomatic toxicity than, an anthracycline containing regimen for the treatment of advanced breast cancer
Molecular motion in cell membranes: analytic study of fence-hindered random walks
A theoretical calculation is presented to describe the confined motion of
transmembrane molecules in cell membranes. The study is analytic, based on
Master equations for the probability of the molecules moving as random walkers,
and leads to explicit usable solutions including expressions for the molecular
mean square displacement and effective diffusion constants. One outcome is a
detailed understanding of the dependence of the time variation of the mean
square displacement on the initial placement of the molecule within the
confined region. How to use the calculations is illustrated by extracting
(confinement) compartment sizes from experimentally reported published
observations from single particle tracking experiments on the diffusion of
gold-tagged G-protein coupled mu-opioid receptors in the normal rat kidney cell
membrane, and by further comparing the analytical results to observations on
the diffusion of phospholipids, also in normal rat kidney cells.Comment: 10 pages, 5 figure
Sphingosine and dihydrosphingosine as biomarkers for multiple sclerosis identified by metabolomic profiling using coupled UPLC-MS
The project aim was to identify differences in the metabolomic profiles in the serum of patients with multiple sclerosis (MS), those with neuropathic pain (NP) and those with both MS and NP compared with controls and to identify potential biomarkers of each disease state. Metabolomic profiling was performed using ultra-high-performance liquid chromatography coupled to mass spectrometry and the data analysis involved parametric methods, principal component analysis, and discriminating filter analysis to determine the differences between disease and control serum samples. Sphingosine and dihydrosphingosine were identified as significant biomarkers
Heterogeneous response and progression patterns reveal phenotypic heterogeneity of tyrosine kinase inhibitor response in metastatic renal cell carcinoma
SC was funded by fellowships from NIHR and Cancer Research UK. IK was
funded by the UCLH Experimental Cancer Centre and UCLH NIHR Biomedical
Research Centre. TP was funded by grants from Cancer Research UK (the
Experimental Cancer Medicine Centre). MG was funded by grants from
Cancer Research UK, Prostate Cancer UK, the Prostate Cancer Foundation,
the Schottlander Research Charitable Trust, the Royal Marsden NIHR
Biomedical Research Centre for Cancer and the Wellcome Trust (grant
number: 105104/Z/14/Z
Meta-analysis of clodronate and breast cancer survival
Clinical trials have reported conflicting results on whether oral clodronate therapy improves survival in breast cancer patients. This study was undertaken to evaluate further the effect of oral clodronate therapy on overall survival, bone metastasis-free survival and nonskeletal metastasis-free survival among breast cancer patients. An extensive literature search was undertaken for the period 1966 to July 2006 to identify clinical trials examining survival in breast cancer patients who received 2 or 3 years of oral clodronate therapy at 1600 mg day−1 compared with those without therapy. Meta-analyses were carried out separately for patients diagnosed with advanced breast cancer and early breast cancer. Our meta-analysis found no evidence of any statistically significant difference in overall survival, bone metastasis-free survival or nonskeletal metastasis-free survival in advanced breast cancer patients receiving clodronate therapy or early breast cancer patients receiving adjuvant clodronate treatment compared with those who did not receive any active treatment
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