Oncogenic RAS promotes production of reactive oxygen species (ROS), which mediate pro-malignant signaling but can also trigger DNA damage-induced tumor suppression. Thus RAS-driven tumor cells require redox-protective mechanisms to mitigate the damaging aspects of ROS. Here we show that MutT Homolog 1 (MTH1), the mammalian 8-oxodGTPase that sanitizes oxidative damage in the nucleotide pool, is important for maintaining several KRAS-driven pro-malignant traits in a nonsmall cell lung carcinoma (NSCLC) model. MTH1 suppression in KRAS-mutant NSCLC cells impairs proliferation and xenograft tumor formation. Furthermore, MTH1 levels modulate KRAS-induced transformation of immortalized lung epithelial cells. MTH1 expression is upregulated by oncogenic KRAS and correlates positively with high KRAS levels in NSCLC human tumors. At a molecular level, in p53-competent KRAS-mutant cells, MTH1 loss provokes DNA damage and induction of oncogene-induced senescence (OIS). In p53-nonfunctional KRAS-mutant cells, MTH1 suppression does not produce DNA damage but induces a reduced proliferative rate and an adaptive decrease in KRAS expression levels. Thus, MTH1 not only enables evasion of oxidative DNA damage and its consequences but can also function as a molecular rheostat for maintaining oncogene expression at optimal levels. Accordingly, our results indicate MTH1 is a novel and critical component of oncogenic KRAS-associated malignancy and its inhibition is likely to yield significant tumor-suppressive outcomes in KRAS-driven tumors.

Perceived barriers and facilitators to physical activity in men with prostate cancer: possible influence of androgen deprivation therapy. AbstractWhile physical activity is beneficial for men with prostate cancer, too few perform sufficient activity for such benefit. This study examined perceptions of men with prostate cancer of their barriers and facilitators to physical activity, and how androgen deprivation therapy (ADT) may influence these perceptions. Two focus groups were conducted, involving 6 ADT and 8 non-ADT patients, respectively. Data was transcribed verbatim and themes developed using a general inductive thematic approach. Facilitators to physical activity common to both groups of cancer survivors included clinician and spousal involvement, with pre-existing comorbidities and increased age cited as barriers by both groups. The ADT sub-group cited personal involvement as a facilitator to physical activity, with fatigue, reduced motivation and a relative lack of specific advice from their clinician as additional barriers. The non-ADT sub-group had no additional facilitators to physical activity but cited time constraints as a barrier. These results highlight the important role that cancer clinicians and spouses play in promoting physical activity for men with prostate cancer and how ADT may influence their other facilitators and barriers. As physical activity is beneficial for prostate cancer survivors, especially those on ADT, cancer clinicians should regularly discuss physical activity with their patients.

BackgroundRegular physical activity is beneficial in both the prevention and management of chronic health conditions. A large proportion of adult New Zealanders, however, are insufficiently active. To help increase population levels of physical activity in New Zealand the Green Prescription, a primary care physical activity scripting program, was developed. The primary aim of this study was to identify why general practitioners (GPs) counsel for physical activity and administer Green Prescriptions. A secondary aim was to examine GPs' views and experiences of Green Prescription counselling for the management of depression.MethodsIndividual face-to-face interviews were conducted with 15 GPs. All interviews were audio-taped and transcribed. Data were analysed using an inductive thematic approach.ResultsSeveral themes and sub-themes emerged from the data. Notably, GPs counselled for physical activity and prescribed Green Prescriptions for both primary preventive (e.g., weight control) and secondary management (e.g., diabetes management) purposes. GPs reported the benefits of the Green Prescription centred around two main themes: (i) a non-medication approach to a healthier lifestyle and (ii) the support benefits of physical activity. Time constraints within the consultation was the only main theme that emerged regarding the barriers GPs perceived to Green Prescription use. Physical activity in general, and physical activity prescribed through the Green Prescription, were also viewed by GPs as beneficial for the management of depression.ConclusionsThe results of this study suggest that New Zealand GPs view the Green Prescription program as beneficial for their patients with pre-existing conditions and/or weight problems. While this is encouraging, the Green Prescription may also be used to promote physical activity in currently healthy but low-active and sedentary individuals. Such individuals are currently disease free, but are at risk for future health-related problems because of their inactive lifestyle. It is recommended that time constraints of the consultation in regard to administering Green Prescriptions could be dealt with by delegating the more time consuming tasks to the patient support counsellors that support the Green Prescription program, and having practice nurses assist in the administration of Green Prescriptions. Green Prescription counselling in conjunction with antidepressant medication may be beneficial for the management of depression and warrants further research.

In recent years the complex process of managing services for patients requiring emergency care has been increasingly under scrutiny and considerable diversity has arisen in the organization of emergency care in both hospital and community settings. One innovation which has been particularly widespread is the development of Emergency Nurse Practitioners (ENPs): experienced Accident and Emergency nurses who assume entire responsibility for patients with minor injuries, in emergency settings. The present paper reports on a study which compared patients' satisfaction with care given by Emergency Nurse Practitioners with that provided by doctors and nurses working together in a traditional A & E. Patients were significantly more likely to have received health education and first aid advice from an ENP than from a doctor. They were also significantly more likely to have been given written instructions to take home and told whom to contact if they needed more help and advice following discharge. Those seen by an ENP also reported that they were subsequently significantly less worried about their health, than did patients seen in a traditional A & E.