The role of osteoblasts in bone metastasis

The primary role of osteoblasts is to lay down new bone during skeletal development and remodelling. Throughout this process osteoblasts directly interact with other cell types within bone, including osteocytes and haematopoietic stem cells. Osteoblastic cells also signal indirectly to bone-resorbing osteoclasts via the secretion of RANKL. Through these mechanisms, cells of the osteoblast lineage help retain the homeostatic balance between bone formation and bone resorption. When tumour cells disseminate in the bone microenvironment, they hijack these mechanisms, homing to osteoblasts and disrupting bone homeostasis. This review describes the role of osteoblasts in normal bone physiology, as well as interactions between tumour cells and osteoblasts during the processes of tumour cell homing to bone, colonisation of this metastatic site and development of overt bone metastases

NF‐κB1, NF‐κB2 and c‐Rel differentially regulate susceptibility to colitis‐associated adenoma development in C57BL/6 mice

NF‐κB signalling is an important factor in the development of inflammation‐associated cancers. Mouse models of Helicobacter‐induced gastric cancer and colitis‐associated colorectal cancer have demonstrated that classical NF‐κB signalling is an important regulator of these processes. In the stomach, it has also been demonstrated that signalling involving specific NF‐κB proteins, including NF‐κB1/p50, NF‐κB2/p52, and c‐Rel, differentially regulate the development of gastric pre‐neoplasia. To investigate the effect of NF‐κB subunit loss on colitis‐associated carcinogenesis, we administered azoxymethane followed by pulsed dextran sodium sulphate to C57BL/6, Nfkb1−/−, Nfkb2−/−, and c‐Rel−/−mice. Animals lacking the c‐Rel subunit were more susceptible to colitis‐associated cancer than wild‐type mice, developing 3.5 times more colonic polyps per animal than wild‐type mice. Nfkb2−/− mice were resistant to colitis‐associated cancer, developing fewer polyps per colon than wild‐type mice (median 1 compared to 4). To investigate the mechanisms underlying these trends, azoxymethane and dextran sodium sulphate were administered separately to mice of each genotype. Nfkb2−/− mice developed fewer clinical signs of colitis and exhibited less severe colitis and an attenuated cytokine response compared with all other groups following DSS administration. Azoxymethane administration did not fully suppress colonic epithelial mitosis in c‐Rel−/− mice and less colonic epithelial apoptosis was also observed in this genotype compared to wild‐type counterparts. These observations demonstrate different functions of specific NF‐κB subunits in this model of colitis‐associated carcinogenesis. NF‐κB2/p52 is necessary for the development of colitis, whilst c‐Rel‐mediated signalling regulates colonic epithelial cell turnover following DNA damage

What is the optimal management of recurrent non-functioning pituitary adenoma?

Recurrent non-functioning pituitary adenomas (NFPAs) pose a di!cult challenge to neurosurgeons. NFPAs do not secrete hormones and thus symptoms usually manifest later in the disease process when the adenoma has reached a su!cient size as to cause mass effect on neighbouring bodies. Treatment of pituitary adenoma is commonly surgical with a transnasal, transsphenoidal approach. Growth of the NFPA into adjacent structures can add to the challenge of surgical resection and thus resection of NFPAs is sometimes incomplete. This often leads to recurrence and necessitates further treatment. A variety of treatment strategies may be employed to design an optimal treatment algorithm, and often a combination of these may be used depending on the size and location of the adenoma and age of the patient. This paper aims to present the evidence for each treatment strategy and to guide what the optimal treatment of NFPA may be, faced with the variety of outcomes that may arise from initial treatment

Voicing the professional doctorate and the researching professional's identity: Theorizing the EdD's uniqueness

Although there is increasing interest in how learning to become a researching professional is understood by students undertaking a professional doctorate of education (EdD), the topic remains under-researched and under-theorized. In this article, we provide a set of theorizations, starting with the purpose and distinctiveness of the professional doctorate and the researching professional identity as this is understood by students and staff participating in the EdD programme in one university in the United Kingdom (UK). This is followed by a retheorization of the researching professional as they develop a reflexive disposition to connect the workplace and the university as the subject and object of the same critical stance. We explore: how the professional doctorate may be understood as practices of diverse researching professionals at different phases and stages of their doctoral journey; the imperative of critical reflexivity as one moves from practitioner to researching professional; and the placing of 'practice' at the nexus of the workplace, the university (doctoral programme) and leading professional change. We conclude with a merging of theorizations building on the being and doing of reflexive practice by EdD doctoral educators/supervisors and doctoral students/researching professionals. Our theorizations are drawn from insights arising from recent EdD research projects (Burnard et al., 2016; Burnard et al., 2018; Heaton et al., forthcoming), and highlighted by narratives from two EdD students currently on a part-time EdD programme

A qualitative study of illness identity: schizophrenia and depression

Illness identity refers to the interpretation of having mental illness in persons who regard themselves as mentally ill. Illness identity can impact people diagnosed with mental illness negatively. However, little is known about the background of illness identity. This study aimed to investigate the process whereby mental health service users accept their diagnosis and develop an illness identity and to compare the processes between schizophrenia and depression. Twenty persons with schizophrenia and depression were interviewed, and the data were analysed using grounded theory approach. The major findings were as follows: i) while those with schizophrenia were shocked by their diagnosis and took time to accept it, this was not true for those with depression; ii) for participants with depression, it was relatively easy to accept their diagnosis, as they thought that depression was a normal illness; participants with schizophrenia needed to learn about their illness, know the efficacy of psychiatric medication and reduce their prejudice against mental illness to accept their diagnosis; and iii) participants’ illness identity encompassed sickness and normality with sickness being related to taking psychiatric medication and normality being associated with having regular work, acting as other people do or living in the community. These findings suggest the influence of social attitudes to each illness on illness identity and the complex nature of illness identity

A single administration of combination therapy inhibits breast tumour progression in bone and modifies both osteoblasts and osteoclasts

We have previously shown that repeated sequential administration of doxorubicin, followed 24 h later by zoledronic acid, inhibits tumour growth in models of established breast cancer bone metastasis. As breast cancer patients only receive zoledronic acid every 3-4 weeks, the aim of the current study was to establish the anti-tumour and bone effects of a single administration of doxorubicin/zoledronic acid combination therapy in a bone metastasis model. MDA-MB-231-GFP cells were injected i.c. in 6-week-old nude mice. On day 2, animals received PBS, doxorubicin (2 mg/kg i.v.), zoledronic acid (100 μg/kg s.c.) or doxorubicin followed 24 h later by zoledronic acid. Anti-tumour effects were assessed on days 15/23 by quantification of apoptotic and proliferating cells and changes in expression of genes implicated in apoptosis, proliferation and bone turnover. Bone effects were assessed by μCT analysis, bone histomorphometry and measurement of serum markers. A tumour-free control group was included. Combination treatment reduced bone tumour burden compared to single agent or PBS control and increased levels of tumour cell apoptosis on day 15, but this was no longer detectable on day 23. Animals receiving zoledronic acid had increased bone density, without evidence of tumour-induced lesions. Bone histomorphometry showed that zoledronic acid caused a decrease in osteoblast and osteoclast numbers and an increase in osteoclast size, in both tumour-free and tumour-bearing animals. Our data show that although zoledronic acid modifies the bone microenvironment through effects on both osteoblasts and osteoclasts, this does not result in a significant anti-tumour effect in the absence of doxorubicin. © 2012 Elsevier GmbH. All rights reserved

Factors affecting the quantity of social interactions and aggression in captive group housed Asiatic black bears (Ursus thibetanus)

This study observed a group of Asiatic black bears (Ursus thibetanus) in a captive environment that differs greatly to standard zoological institutions. Rather than being housed alone or with one other, as is typical in captivity, two large groups of bears consisting of 24 individuals were observed in two different enclosures. Any instance of social behaviour was noted down, both positive and negative, to determine the extent to which social relationships form and whether these animals have the capacity to live in large groups, regardless of their supposed solitary nature. The results indicated that the duration of social interactions were longer in the smaller group of bears but there was a higher number of instigators in the larger group. Generalised Linear Model analysis showed that interactions, both positive and negative, occurred less in the mornings, particularly during feeding time while an increase in aggression was noted generally prior to afternoon feeding (P = 0.001). Female-female aggression was much more prominent than between males or males and females. It appears that despite being defined as solitary, this species benefits greatly from social interaction with others of its kind when housed in captivity