Pancreatic cancer cachexia: a review of mechanisms and therapeutics.

Over the last decade, we have gained new insight into the pathophysiology of cachexia associated with pancreatic cancer. Unfortunately, its treatment is complex and remains a challenge. Pancreatic cancer cachexia is a multifactorial syndrome characterized by uncompensated adipose tissue and skeletal muscle loss in the setting of anorexia that leads to progressive functional impairment. This paper will review the current concepts of pancreatic cancer cachexia, its assessment and pathophysiology as well as current and future treatments. The successful management of pancreatic cancer cachexia will likely require a multimodal approach that includes nutritional support and combination pharmaceutical interventions

Translation factor eIF5a is essential for IFNγ production and cell cycle regulation in primary CD8 T lymphocytes

Control of mRNA translation adjusts protein production rapidly and facilitates local cellular responses to environmental conditions. Traditionally initiation of translation is considered to be a major translational control point, however, control of peptide elongation is also important. Here we show that the function of the elongation factor, eIF5a, is regulated dynamically in naïve CD8(+) T cells upon activation by post-translational modification, whereupon it facilitates translation of specific subsets of proteins. eIF5a is essential for long-term survival of effector CD8(+) T cells and sequencing of nascent polypeptides indicates that the production of proteins which regulate proliferation and key effector functions, particularly the production of IFNγ and less acutely TNF production and cytotoxicity, is dependent on the presence of functional eIF5a. Control of translation in multiple immune cell lineages is required to co-ordinate immune responses and these data illustrate that translational elongation contributes to post-transcriptional regulons important for the control of inflammation

Perceptions and Barriers of Survivorship Care in Asia: Perceptions From Asian Breast Cancer Survivors.

PurposeWith the long-term goal to optimize post-treatment cancer care in Asia, we conducted a qualitative study to gather in-depth descriptions from multiethnic Asian breast cancer survivors on their perceptions and experiences of cancer survivorship and their perceived barriers to post-treatment follow-up.MethodsTwenty-four breast cancer survivors in Singapore participated in six structured focus group discussions. The focus group discussions were voice recorded, transcribed verbatim, and analyzed by thematic analysis.ResultsBreast cancer survivors were unfamiliar with and disliked the term "survivorship," because it implies that survivors had undergone hardship during their treatment. Cognitive impairment and peripheral neuropathy were physical symptoms that bothered survivors the most, and many indicated that they experienced emotional distress during survivorship, for which they turned to religion and peers as coping strategies. Survivors indicated lack of consultation time and fear of unplanned hospitalization as main barriers to optimal survivorship care. Furthermore, survivors indicated that they preferred receipt of survivorship care at the specialty cancer center.ConclusionBudding survivorship programs in Asia must take survivor perspectives into consideration to ensure that survivorship care is fully optimized within the community

Roles and recommendations from primary care physicians towards managing low-risk breast cancer survivors in a shared-care model with specialists in Singapore-a qualitative study.

BackgroundBreast cancer is prevalent and has high cure rates. The resultant increase in numbers of breast cancer survivors (BCS) may overwhelm the current oncology workforce in years to come. We postulate that primary care physicians (PCPs) could play an expanded role in comanaging survivors, provided they are given the appropriate tools and training to do so.ObjectiveTo explore the perspectives of PCPs towards managing BCS in a community-based shared-care programme with oncologists.MethodsEleven focus groups and six in-depth interviews were conducted with seventy PCPs recruited by purposive sampling. All sessions were audio-recorded, transcribed verbatim and coded by three independent investigators. Thematic data analysis was performed and the coding process facilitated by NVivo 12.ResultsMajority of PCPs reported currently limited roles in managing acute and non-cancer issues, optimizing comorbidities and preventive care. PCPs aspired to expand their role to include cancer surveillance, risk assessment and addressing unmet psychosocial needs. PCPs preferred to harmonize cancer survivorship management of their primary care patients who are also BCS, with defined role distinct from oncologists. Training to understand the care protocol, enhancement of communication skills, confidence and trust were deemed necessary. PCPs proposed selection criteria of BCS and adequacy of their medical information; increased consultation time; contact details and timely access to oncologists (if needed) in the shared-care programme.ConclusionsPCPs were willing to share the care of BCS with oncologists but recommended role definition, training, clinical protocol, resources and access to oncologist's consultation to optimize the programme implementation

Analysis of Nkx3.1:Cre-driven Erk5 deletion reveals a profound spinal deformity which is linked to increased osteoclast activity

Extracellular signal-regulated protein kinase 5 (ERK5) has been implicated during development and carcinogenesis. Nkx3.1-mediated Cre expression is a useful strategy to genetically manipulate the mouse prostate. While grossly normal at birth, we observed an unexpected phenotype of spinal protrusion in Nkx3.1:Cre;Erk5fl/fl (Erk5fl/fl) mice by ~6–8 weeks of age. X-ray, histological and micro CT (µCT) analyses showed that 100% of male and female Erk5fl/fl mice had a severely deformed curved thoracic spine, with an associated loss of trabecular bone volume. Although sex-specific differences were observed, histomorphometry measurements revealed that both bone resorption and bone formation parameters were increased in male Erk5fl/fl mice compared to wild type (WT) littermates. Osteopenia occurs where the rate of bone resorption exceeds that of bone formation, so we investigated the role of the osteoclast compartment. We found that treatment of RANKL-stimulated primary bone marrow-derived macrophage (BMDM) cultures with small molecule ERK5 pathway inhibitors increased osteoclast numbers. Furthermore, osteoclast numbers and expression of osteoclast marker genes were increased in parallel with reduced Erk5 expression in cultures generated from Erk5fl/fl mice compared to WT mice. Collectively, these results reveal a novel role for Erk5 during bone maturation and homeostasis in vivo

Enabling quantitative data analysis through e-infrastructures

This paper discusses how quantitative data analysis in the social sciences can engage with and exploit an e-Infrastructure. We highlight how a number of activities which are central to quantitative data analysis, referred to as ‘data management’, can benefit from e-infrastructure support. We conclude by discussing how these issues are relevant to the DAMES (Data Management through e-Social Science) research Node, an ongoing project that aims to develop e-Infrastructural resources for quantitative data analysis in the social sciences