Antiangiogenic gene therapy of cancer: recent developments

With the role of angiogenesis in tumor growth and progression firmly established, considerable effort has been directed to antiangiogenic therapy as a new modality to treat human cancers. Antiangiogenic agents have recently received much widespread attention but strategies for their optimal use are still being developed. Gene therapy represents an attractive alternative to recombinant protein administration for several reasons. This review evaluates the potential advantages of gene transfer for antiangiogenic cancer therapy and describes preclinical gene transfer work with endogenous angiogenesis inhibitors demonstrating the feasibility of effectively suppressing and even eradicating tumors in animal models. Additionally, we describe the advantages and disadvantages of currently available gene transfer vectors and update novel developments in this field. In conclusion, gene therapy holds great promise in advancing antiangiogenesis as an effective cancer therapy and will undoubtedly be evaluated in human clinical trials in the near future

Characterization of the ion transport responses to ADH in the MDCK-C7 cell line

The Madin-Darby canine kidney (MDCK) cell line expresses many characteristics of the renal collecting duct. The MDCK-C7 subclone forms a high-resistance, hormone-responsive model of the principal cells, which are found in distal sections of the renal tubule. The electrophysiological technique of short-circuit current measurement was used to examine the response to antidiuretic hormone (ADH) in the MDCK-C7 clone. Three discrete electrogenic ion transport phenomena can be distinguished temporally and by the use of inhibitors and effectors. Initially the cells exhibit anion secretion through the cystic fibrosis transmembrane conductance regulator (CFTR). The presence of CFTR was confirmed by immunoprecipitation followed by Western blotting. The CFTR-mediated anion secretion is transient and is followed, in time, by a verapamil- and Ba(+)-sensitive anion secretion or cation absorption and, finally, by Na+ reabsorption via epithelial Na+ channels (ENaC). In contrast to other studies of MDCK cells, we see no indication that the presence of CFTR functionally inhibits ENaC. The characterization of the various ion transport phenomena substantiates this cell line as a model renal epithelium that can be used to study the hormonal and metabolic regulation of ion transport

PPARγ agonists do not directly enhance basal or insulin-stimulated Na+ transport via the epithelial Na+ channel

Selective agonists of peroxisome proliferator-activated receptor gamma (PPARgamma) are anti-diabetic drugs that enhance cellular responsiveness to insulin. However, in some patients, fluid retention, plasma volume expansion, and edema have been observed. It is well established that insulin regulates Na(+) reabsorption via the epithelial sodium channel (ENaC) located in the distal tubule. Therefore, we hypothesized that these agonists may positively modulate insulin-stimulated ENaC activity leading to increased Na(+) reabsorption and fluid retention. Using electrophysiological techniques, dose-response curves for insulin-mediated Na(+) transport in the A6, M-1, and mpkCCD(cl4) cell lines were performed. Each line demonstrated hormone efficacy within physiological concentration ranges and, therefore, can be used to monitor clinically relevant effects of pharmacological agents which may affect electrolyte transport. Immunodetection and quantitative PCR analyses showed that each cell line expresses viable and functional PPARgamma receptors. Despite this finding, two PPARgamma agonists, pioglitazone and GW7845 did not directly enhance basal or insulin-stimulated Na(+) flux via ENaC, as shown by electrophysiological methodologies. These studies provide important results, which eliminate insulin-mediated ENaC activation as a candidate mechanism underlying the fluid retention observed with PPARgamma agonist use

Is there a role for sentinel lymph node biopsy in the management of sarcoma?

A review of the role for sentinel lymph node biopsy in sarcoma.Is there a role for sentinel lymph node (SLN) biopsy in the management of sarcoma? Sentinel node biopsy has dramatically changed the management of melanoma and breast cancer, helping surgeons avoid radical lymphadenectomies in node negative patients who would previously have undergone a more morbid operation with little benefit, or remained pathologically unstaged. Many investigators have explored the use of lymphatic mapping for malignancies other than breast cancer or melanoma. Lymphatic mapping and sentinel node biopsy has not been investigated in the management of sarcomas, which is not surprising given that the majority of sarcomas spread by local extension or hematogenously. Regional lymph node metastases are rare; developing in about 3–10% of patients with localized disease. However, among certain subtypes of high-grade sarcomas there is a propensity for regional lymph node metastases. These include rhabdomyosarcoma, epithelioid sarcoma, clear cell sarcoma, synovial sarcoma, and vascular sarcomas. It is in these particular subtypes that there may be a benefit to SLN biopsy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/39196/1/sarcoma SLN.pd

Surgical Therapy of Cutaneous Melanoma

For most solid tumors, therapy has evolved from surgery alone to a multidisciplinary approach. Malignant melanoma remains an exception, with surgery maintaining the principal role not only for treatment of the primary lesion but also staging and the management of advanced disease. The surgical management of melanoma has evolved over the years, resulting in a substantial decrease in the morbidity associated with treatment wihtout a compromise in outcome. This article will review the changes that have occured leading to the current surgical approach to melanoma, the evidence behind these recommendations, and new questions that need to be addressed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/51541/1/Surgical Therapy of Cutaneous Melanoma.pd

Guided self-help concreteness training as an intervention for major depression in primary care: a Phase II randomized controlled trial

addresses: Mood Disorders Centre, University of Exeter, UK. [email protected]: PMCID: PMC3359637Copyright © Cambridge University Press 2011 The online version of this article is published within an Open Access environment subject to the conditions of the Creative Commons Attribution-NonCommercial-ShareAlike licence . The written permission of Cambridge University Press must be obtained for commercial re-use. DOI: http://dx.doi.org/10.1017/S0033291711002480The development of widely accessible, effective psychological interventions for depression is a priority. This randomized trial provides the first controlled data on an innovative cognitive bias modification (CBM) training guided self-help intervention for depression

Delivering information and brief advice on alcohol (IBA) in social work and social care settings: an exploratory study

Social workers and practitioners working in social care are potentially key players in the prevention of alcohol-related harm and harm reduction for people using services and their carers. This requires attention to workforce development alongside the selection of appropriate tools to support prevention strategies. We report findings from a UK exploratory study into the potential of using Identification and Brief Advice (IBA) as a tool for screening and prevention in social work and social care settings. Thirty-six social workers and social care practitioners attended one of two training workshops on IBA in the South East of England. Pre and post-workshop surveys (n = 35 and n = 20, respectively) and four post-workshop focus groups (n = 36) were conducted with participants to explore the application of IBA taking into account the paradigmatic shift towards prevention and holistic approaches indicated in recent UK legislation and policy. Four themes emerged from the findings: (1) perceptions of the social work/social care role in responding to alcohol problems, (2) ethical concerns, (3) time conflicts and problems of delivering IBA and (4) the role of training. Further studies are needed to evaluate the effectiveness of motivational techniques and tools that social workers can use to promote preventative practise for alcohol-related harm. Different strategies are required to engage and support those working in social care to increase proactive engagement with problematic alcohol use in everyday practise settings

Barriers and facilitators to adherence to group exercise in institutionalized older people living with dementia: a systematic review

Objectives Research suggests targeted exercise is important for people living with dementia, especially those living in residential care. The aim of this review was to collect and synthesize evidence on the known barriers and facilitators to adherence to group exercise of institutionalized older people living with dementia. Methods We searched all available electronic databases. Additionally, we searched trial registries (clinicaltrial.gov, and WHO ICTRP) for ongoing studies. We searched for and included papers from January 1990 until September 2017 in any language. We included randomized, non-randomized trials. Studies were not eligible if participants were either healthy older people or people suffering from dementia but not living in an institution. Studies were also excluded if they were not focused on barriers and facilitators to adherence to group exercise. Results Using narrative analysis, we identified the following themes for barriers: bio-medical reasons and mental wellbeing and physical ability, relationships dynamics, and socioeconomic reasons. The facilitators were grouped under the following thematic frames: bio-medical benefits and benefits related to physical ability, feelings and emotions and confidence improvements, therapist and group relationships dynamics and activity related reasons. Conclusions We conclude that institutionalized older people living with dementia, even those who are physically frail, incontinent and/or have mild dementia can demonstrate certain level of exercise adherence, and therefore can respond positively to exercise programs. Tailored, individually-adjusted and supported physical activity, led by a knowledgeable, engaging and well communicating therapist/facilitator improves the adherence to group exercise interventions of institutionalized older people living with dementia

Developing a community based psychosocial intervention with older people and third sector workers for anxiety and depression: a qualitative study

Background: One-in-five people in the UK experience anxiety and/or depression in later life. However, anxiety and depression remain poorly detected in older people, particularly in those with chronic physical ill health. In the UK, a stepped care approach, to manage common mental health problems, is advocated which includes service provision from non-statutory organisations (including third/voluntary sector). However, evidence to support such provision, including the most effective interventions, is limited. The qualitative study reported here constitutes the first phase of a feasibility study which aims to assess whether third sector workers can deliver a psychosocial intervention to older people with anxiety and/or depression. The aim of this qualitative study is to explore the views of older people and third sector workers about anxiety and depression among older people in order to refine an intervention to be delivered by third sector workers. Methods: Semi-structured interviews with participants recruited through purposive sampling from third sector groups in North Staffordshire. Interviews were digitally recorded with consent, transcribed and analysed using principles of constant comparison. Results: Nineteen older people and 9 third sector workers were interviewed. Key themes included: multiple forms of loss, mental health as a personal burden to bear, having courage and providing/receiving encouragement, self- worth and the value of group activities, and tensions in existing service provision, including barriers and gaps. Conclusions: The experience of loss was seen as central to feelings of anxiety and depression among community- dwelling older people. This study contributes to the evidence pointing to the scale and severity of mental health needs for some older people which can arise from multiple forms of loss, and which present a significant challenge to health, social care and third sector services. The findings informed development of a psychosocial intervention and training for third sector workers to deliver the intervention