Poor myeloid engraftment remains a barrier to experimental use of humanized mice. Focusing primarily on peripheral blood cells, we compared the engraftment profile of NOD-scid-IL2Rγc−/− (NSG) mice with that of NSG mice transgenic for human membrane stem cell factor (hu-mSCF mice), NSG mice transgenic for human interleukin (IL)-3, granulocyte-macrophage-colony stimulating factor (GM-CSF), and stem cell factor (SGM3 mice). hu-mSCF and SGM3 mice showed enhanced engraftment of human leukocytes compared to NSG mice, and this was reflected in the number of human neutrophils and monocytes present in these strains. Importantly, discrete classical, intermediate, and nonclassical monocyte populations were identifiable in the blood of NSG and hu-mSCF mice, while the nonclassical population was absent in the blood of SGM3 mice. Granulocyte-colony stimulating factor (GCSF) treatment increased the number of blood monocytes in NSG and hu-mSCF mice, and neutrophils in NSG and SGM3 mice; however, this effect appeared to be at least partially dependent on the stem cell donor used to engraft the mice. Furthermore, GCSF treatment resulted in a preferential expansion of nonclassical monocytes in both NSG and hu-mSCF mice. Human tubulointerstitial CD11c+ cells were present in the kidneys of hu-mSCF mice, while monocytes and neutrophils were identified in the liver of all strains. Bone marrow-derived macrophages prepared from NSG mice were most effective at phagocytosing polystyrene beads. In conclusion, hu-mSCF mice provide the best environment for the generation of human myeloid cells, with GCSF treatment further enhancing peripheral blood human monocyte cell numbers in this strain.
Triple negative breast cancer (TNBC) is a breast cancer subtype which is particularly aggressive and invasive. The treatment of TNBC has been limited due to the lack of well-defined molecular targets. Exosomes are nano-sized extracellular vesicles that are released from virtually all cell types into the extracellular space. Due to their endocytic origin, exosomes carry valuable information from their cells of origin. Exosomes were first thought to serve as "garbage disposals" that eliminate unwanted cellular components. Later, they were found to be involved in the pathology of many diseases including cancer. Despite their established roles in multiple diseases, only a small number of studies have focused on the role of exosomes in TNBC. In this review, we outline the roles of exosomes in cancer progression, metastasis and drug resistance in this breast cancer subtype. We then further illustrate the potential roles of exosomes as diagnostic tools, therapeutic targets and delivery systems.
Bovine besnoitiosis, caused by the apicomplexan protozoan parasite Besnoitia besnoiti , was diagnosed in an Irish dairy herd. This is the first diagnosis of besnoitiosis in Ireland or the UK and the most northerly European outbreak yet described. The diagnosis occurred following a farm investigation in June 2015 into an unusual dermatological problem that had been ongoing since 2010. On an annual basis, 1–2 per cent of cows in the herd exhibited clinical signs, including skin thickening, alopecia, weight loss and poor performance. Others displayed pyrexia, limb oedema, respiratory distress and reduced milk yield. Histopathological examination of skin revealed granulomatous and eosinophilic dermatitis, with characteristic intradermal protozoal cysts, consistent with cutaneous besnoitiosis. Follow‐up serological testing and clinical examination of cattle (n=228) on the farm found that 68 per cent (144/212) were seropositive for B. besnoiti . In addition, 51 per cent (117/228) had characteristic scleral conjunctival cysts and 68 per cent (134/198) had vulval cysts. Postmortem examination of a severely affected animal revealed typical gross and histopathological lesions of B. besnoiti infection. These results confirmed endemic infection with B. besnoiti . The identification of this exotic disease highlights the importance of veterinary surveillance at both local and national level, particularly in relation to emerging diseases.
Malignant melanoma, one of the most aggressive human malignancies, is responsible for 80% of skin cancer deaths. Whilst early detection of disease progression or metastasis can improve patient survival, this remains a challenge due to the lack of reliable biomarkers. Importantly, these clinical challenges are not unique to humans, as melanoma affects many other species, including companion animals, such as the dog and horse. Extracellular vesicles (EVs) are tiny nanoparticles involved in cell-to-cell communication. Several protein and genomic EV markers have been described in the literature, as well as a wide variety of methods for isolating EVs from body fluids. As such, they may be valuable biomarkers in cancer and may address some clinical challenges in the management melanoma. This review aimed to explore the translational applications of EVs as biomarkers in melanoma, as well as their role in the clinical setting in humans and animals. A summary of melanoma-specific protein and genomic EV markers is presented, followed by a discussion of the role EVs in monitoring disease progression and treatment response. Finally, herein, we reviewed the advantages and disadvantages of methods utilised to isolate EVs from bodily fluids in melanoma patients (human and animals) and describe some of the challenges that will need to be addressed before EVs can be introduced in the clinical setting.
Five domestic cats were euthanased owing to confirmed or suspected Mycobacterium bovis infection. The initial source of infection remains unclear. Cat A was presented to a veterinary clinic in County Kildare, Ireland, with a discharging submandibular lesion. The infection appears to have been transmitted to four other cats through direct (cats B and C living in the same household as cat A) and non-direct (nosocomial spread during routine operations; cats D and E) contact over a 13.5-week period. Of the five cases, two (B and D) had post-mortem examinations in which gross changes consistent with tuberculosis were seen, moderate numbers of acid-fast bacteria (AFB) were seen on microscopy and M bovis (spoligotype SB0978) was confirmed on culture. Of the remaining three cats, one had a swab taken from its draining ovariohysterectomy wound, which revealed large numbers of AFB with morphology consistent with M bovis (cat E). Two cases were euthanased without diagnostic tests; however, their history and clinical presentations were highly suggestive of tuberculosis (cats A and C). To our knowledge, this is the first documented case of nosocomial spread of M bovis in cats.