The role of Allee effect in modelling post resection recurrence of glioblastoma

Resection of the bulk of a tumour often cannot eliminate all cancer cells, due to their infiltration into the surrounding healthy tissue. This may lead to recurrence of the tumour at a later time. We use a reaction-diffusion equation based model of tumour growth to investigate how the invasion front is delayed by resection, and how this depends on the density and behaviour of the remaining cancer cells. We show that the delay time is highly sensitive to qualitative details of the proliferation dynamics of the cancer cell population. The typically assumed logistic type proliferation leads to unrealistic results, predicting immediate recurrence. We find that in glioblastoma cell cultures the cell proliferation rate is an increasing function of the density at small cell densities. Our analysis suggests that cooperative behaviour of cancer cells, analogous to the Allee effect in ecology, can play a critical role in determining the time until tumour recurrence

Endo180 modulation by bisphosphonates and diagnostic accuracy in metastatic breast cancer

We thank the patients who participated in this study; Professor Gerry Thomas and the Imperial College Healthcare NHS Trust, Human Biomaterials Resource Centre (Tissue Bank); Professor Clare M Isacke (Institute of Cancer Research, London) for Endo180 antibodies; Dr Richard Harvey (Department of Medical Oncology, Imperial College Healthcare NHS Trust) for CA 15-3 antigen measurement. The Division of Cancer at Imperial College London, Imperial College Healthcare NHS Trust is an Experimental Cancer Medicine Centre (ECMC) supported by funds from Cancer Research UK and the Department of Health (C37/A7283) and forms part of Imperial Cancer Research UK Centre (C42671/A12196). CP is recipient of a CRUK Clinician Scientist award. JW is The Flow Foundation Professor of Oncology at Imperial College London. MPC and GK were supported by donations from Tony and Rita Gallagher and Imperial College NHS Healthcare Trust Special Trustees (to JW and JS). MPC was funded by The Rosetrees Trust (Grant JS16/M59; to JW and JS). A-VF was funded by Fundação para a Ciência e Tecnologia fellowship (project supervisor: JS) and Imperial College NHS Healthcare Special Trustees (to JW and JS). MR-T was funded by the Association of International Cancer Research (Grant 08-0803 to JS)

Endo180 modulation by bisphosphonates and diagnostic accuracy in metastatic breast cancer

Background:Endo180 (CD280; MRC2; uPARAP)-dependent collagen remodelling is dysregulated in primary tumours and bone metastasis. Here, we confirm the release and diagnostic accuracy of soluble Endo180 for diagnosing metastasis in breast cancer (BCa).Methods:Endo180 was quantified in BCa cell conditioned medium and plasma from BCa patients stratified according to disease status and bisphosphonate treatment (n=88). All P-values are from two-sided tests.Results:Endo180 is released by ectodomain shedding from the surface of MCF-7 and MDA-MB-231 BCa cell lines. Plasma Endo180 was significantly higher in recurrent/metastatic (1.71±0.87; n=59) vs early/localised (0.92±0.37; n=29) BCa (P<0.0001). True/false-positive rates for metastasis classification were: 85%/50% for the reference standard, CA 15-3 antigen (28 U ml-1); 97%/36% for Endo180; and 97%/32% for CA 15-3 antigen+Endo180. Bisphosphonate treatment was associated with reduced Endo180 levels in BCa patients with bone metastasis (P=0.011; n=42). True/false-positive rates in bisphosphonate-naive patients (n=57) were: 68%/45% for CA 15-3 antigen; 95%/20% for Endo180; and 92%/21% for CA 15-3 antigen+Endo180.Conclusion:Endo180 is a potential marker modulated by bisphosphonates in metastatic BCa

Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Acinetobacter baumannii among horses entering a veterinary teaching hospital: The contemporary "Trojan Horse"

Pathogens frequently associated with multi-drug resistant (MDR) phenotypes, including extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) and Acinetobacter baumannii isolated from horses admitted to horse clinics, pose a risk for animal patients and personnel in horse clinics. To estimate current rates of colonization, a total of 341 equine patients were screened for carriage of zoonotic indicator pathogens at hospital admission. Horses showing clinical signs associated with colic (n = 233) or open wounds (n = 108) were selected for microbiological examination of nostril swabs, faecal samples and wound swabs taken from the open wound group. The results showed alarming carriage rates of Gram-negative MDR pathogens in equine patients: 10.7% (34 of 318) of validated faecal specimens were positive for ESBL-E (94%: ESBL-producing Escherichia coli), with recorded rates of 10.5% for the colic and 11% for the open wound group. 92.7% of the ESBL-producing E. coli were phenotypically resistant to three or more classes of antimicrobials. A. baumannii was rarely detected (0.9%), and all faecal samples investigated were negative for Salmonella, both directly and after two enrichment steps. Screening results for the equine nostril swabs showed detection rates for ESBL-E of 3.4% among colic patients and 0.9% in the open wound group, with an average rate of 2.6% (9/340) for both indications. For all 41 ESBL-producing E. coli isolated, a broad heterogeneity was revealed using pulsed-field gel electrophoresis (PFGE) patterns and whole genome sequencing (WGS) -analysis. However, a predominance of sequence type complex (STC)10 and STC1250 was observed, including several novel STs. The most common genes associated with ESBL-production were identified as blaCTX-M-1 (31/41; 75.6%) and blaSHV-12 (24.4%). The results of this study reveal a disturbingly large fraction of multi-drug resistant and ESBL-producing E. coli among equine patients, posing a clear threat to established hygiene management systems and work-place safety of veterinary staff in horse clinics