Abstract:Osteosarcoma is the most common primary bone tumour in children and adolescents and advanced osteosarcoma patients with evidence of metastasis share a poor prognosis.Osteosarcoma frequently gains resistance to standard therapies highlighting the need for improved treatment regimens and identification of novel therapeutic targets. Cancer stem cells (CSC) represent a sub-type of tumour cells attributed to critical steps in cancer including tumour propagation, therapy resistance, recurrence and in some cases metastasis. Recent published work demonstrates evidence of cancer stem cell phenotypes in osteosarcoma with links to drug resistance and tumorigenesis. In this review we will discuss the commonly used isolation techniques for cancer stem cells in osteosarcoma as well as the identified biochemical and molecular markers.

Purpose: Clinical trials in early breast cancer have suggested that benefits of adjuvant bone-targeted treatments are restricted to women with established menopause. We developed models that mimic pre-and postmenopausal status to investigate effects of altered bone turnover on growth of disseminated breast tumor cells. Here, we report a differential antitumor effect of zoledronic acid (ZOL) in these two settings.Experimental design: Twleve-week-old female Balb/c-nude mice with disseminated MDA-MB-231 breast tumor cells in bone underwent sham operation or ovariectomy (OVX), mimicking the pre-and postmenopausal bone microenvironment, respectively. To determine the effects of bone-targeted therapy, sham/OVX animals received saline or 100 mg/kg ZOL weekly. Tumor growth was assessed by in vivo imaging and effects on bone by real-time PCR, micro-CT, histomorphometry, and measurements of bone markers. Disseminated tumor cells were detected by two-photon microscopy.Results: OVX increased bone resorption and induced growth of disseminated tumor cells in bone. Tumors were detected in 83% of animals following OVX (postmenopausal model) compared with 17% following sham operation (premenopausal model). OVX had no effect on tumors outside of bone. OVX-induced tumor growth was completely prevented by ZOL, despite the presence of disseminated tumor cells. ZOL did not affect tumor growth in bone in the sham-operated animals. ZOL increased bone volume in both groups.Conclusions: This is the first demonstration that tumor growth is driven by osteoclast-mediated mechanisms in models that mimic post-but not premenopausal bone, providing a biologic rationale for the differential antitumor effects of ZOL reported in these settings. Clin Cancer Res; 20(11); 2922-32. Ó2014 AACR.

Although research on the epidemiology and ecology of Ebola has expanded since the 2014–15 outbreak in West Africa, less attention has been paid to the mental health implications and the psychosocial context of the disease for providers working in primary health facilities (rather than Ebola-specific treatment units). This study draws on 54 qualitative interviews with 35 providers working in eight peripheral health units of Sierra Leone's Bo and Kenema Districts. Data collection started near the height of the outbreak in December 2014 and lasted 1 month. Providers recounted changes in their professional, personal and social lives as they became de facto first responders in the outbreak. A theme articulated across interviews was Ebola’s destruction of social connectedness and sense of trust within and across health facilities, communities and families. Providers described feeling lonely, ostracized, unloved, afraid, saddened and no longer respected. They also discussed restrictions on behaviors that enhance coping including attending burials and engaging in physical touch (hugging, handshaking, sitting near, or eating with colleagues, patients and family members). Providers described infection prevention measures as necessary but divisive because screening booths and protective equipment inhibited bonding or ‘suffering with’ patients. To mitigate psychiatric morbidities and maladaptive coping mechanisms—and to prevent the spread of Ebola—researchers and program planners must consider the psychosocial context of this disease and mechanisms to enhance psychological first aid to all health providers, including those in peripheral health settings.

Following the 2013-2016 outbreak of Ebola virus disease (EVD) in West Africa, governments across the region imposed a ban on the hunting and consumption of meat from wild animals. This injunction was accompanied by public health messages emphasising the infectious potential of wild meat, or 'bushmeat.' Using qualitative methods, we examine the local reception and impact of these interventions. Fieldwork was focused in 9 villages in the Eastern and Southern provinces of Sierra Leone between August and December 2015. We conducted 47 semi-structured interviews, coordinated 12 informal group discussions, and conducted direct observations throughout. We also draw from research undertaken in Sierra Leone immediately before the outbreak, and from our participation in the EVD response in Guinea and Sierra Leone. Our findings underscore the social and political reverberations of hunting proscriptions. Messaging that unilaterally stressed the health risk posed by wild meat contradicted the experiences of target publics, who consume wild meat without incident. This epistemic dissonance radically undercut the effectiveness of the ban, which merely served to proliferate informal networks of wild animal trade and sale-rendering the development of acceptable, evidence-based surveillance and mitigation strategies for zoonotic spillovers almost impossible. Further, the criminalisation of wild meat consumption fuelled fears and rumours within communities under considerable strain from the health, social, and economic effects of the epidemic, entrenching distrust towards outbreak responders and exacerbating pre-existing tensions within villages. These unintended consequences are instructive for public health emergency response and preparedness. While wild meat is a risk for zoonotic infection, mitigating those risks entails interventions that fully take into account the local significances of hunting-including a communicative engagement that is designed, validated, and continually refined before emergency situations. Ultimately, our research questions the value of legal sanctions as a means of behavioural change in an emergency context.

Bone sarcomas are tumours belonging to the family of mesenchymal tumours and constitute a highly heterogeneous tumour group. The three main bone sarcomas are osteosarcoma, Ewing sarcoma and chondrosarcoma each subdivided in diverse histological entities. They are clinically characterised by a relatively high morbidity and mortality, especially in children and adolescents. Although these tumours are histologically, molecularly and genetically heterogeneous, they share a common involvement of the local microenvironment in their pathogenesis. This review gives a brief overview of their specificities and summarises the main therapeutic advances in the field of bone sarcoma.