Combinatorial Therapy: Targeting CD133+ Glioma Stem-like Cells with a Polysaccharide-Prodrug Complex Functionalised Gold Nanocages.

Cancer treatments are advancing to harness the body's immune system against tumours, aiming for lasting effects. This progress involves combining potent chemotherapy drugs with immunogens to kill cancer cells and trigger lasting immunity. Developing new prodrugs that integrate both chemotherapy and immune-boosting elements could significantly improve anticancer outcomes by activating multiple mechanisms to kill cancer cells.

The role of mouse tumour models in the discovery and development of anticancer drugs.

Our understanding of cancer biology has increased substantially over the past 30 years. Despite this, and an increasing pharmaceutical company expenditure on research and development, the approval of novel oncology drugs during the past decade continues to be modest. In addition, the attrition of agents during clinical development remains high.

Author Correction: Excitotoxic inactivation of constitutive oxidative stress detoxification pathway in neurons can be rescued by PKD1.

The original version of this Article contained an error in the spelling of the author Álvaro Sebastián-Serrano, which was incorrectly given as Álvaro Sebastián Serrano. This has now been corrected in both the PDF and HTML versions of the Article.

Excitotoxic inactivation of constitutive oxidative stress detoxification pathway in neurons can be rescued by PKD1.

Excitotoxicity, a critical process in neurodegeneration, induces oxidative stress and neuronal death through mechanisms largely unknown. Since oxidative stress activates protein kinase D1 (PKD1) in tumor cells, we investigated the effect of excitotoxicity on neuronal PKD1 activity. Unexpectedly, we find that excitotoxicity provokes an early inactivation of PKD1 through a dephosphorylation-dependent mechanism mediated by protein phosphatase-1 (PP1) and dual specificity phosphatase-1 (DUSP1).

Silencing of protein kinase D2 induces glioma cell senescence via p53-dependent and -independent pathways.

Background: Glioblastoma multiforme (GBM) is a highly aggressive tumor of the central nervous system with a dismal prognosis for affected patients. Aberrant protein kinase C (PKC) signaling has been implicated in gliomagenesis, and a member of the PKC-activated protein kinase D (PRKD) family, PRKD2, was identified as mediator of GBM growth in vitro and in vivo.

Methods: The outcome of PRKD2 silencing and pharmacological inhibition on glioma cell proliferation was established with different glioma cell lines.

Protein kinase D2 regulates migration and invasion of U87MG glioblastoma cells in vitro.

Glioblastoma multiforme (GBM) is the most common malignant brain tumor, which, despite combined modality treatment, reoccurs and is invariably fatal for affected patients. Recently, a member of the serine/threonine protein kinase D (PRKD) family, PRKD2, was shown to be a potent mediator of glioblastoma growth. Here we studied the role of PRKD2 in U87MG glioblastoma cell migration and invasion in response to sphingosine-1-phosphate (S1P), an activator of PRKD2 and a GBM mitogen.

Characterization of the biological effects of a novel protein kinase D inhibitor in endothelial cells.

VEGF (vascular endothelial growth factor) plays an essential role in angiogenesis during development and in disease largely mediated by signalling events initiated by binding of VEGF to its receptor, VEGFR2 (VEGF receptor 2)/KDR (kinase insert domain receptor). Recent studies indicate that VEGF activates PKD (protein kinase D) in endothelial cells to regulate a variety of cellular functions, including signalling events, proliferation, migration and angiogenesis. To better understand the role of PKD in VEGF-mediated endothelial function, we characterized the effects of a novel pyrazine benzamide PKD inhibitor CRT5 in HUVECs (human umbilical vein endothelial cells).

A novel small-molecule inhibitor of protein kinase D blocks pancreatic cancer growth in vitro and in vivo.

Protein kinase D (PKD) family members are increasingly implicated in multiple normal and abnormal biological functions, including signaling pathways that promote mitogenesis in pancreatic cancer. However, nothing is known about the effects of targeting PKD in pancreatic cancer. Our PKD inhibitor discovery program identified CRT0066101 as a specific inhibitor of all PKD isoforms.

Bridging the care continuum: patient information needs for specialist referrals.

Background: Information transfer is critical in the primary care to specialist referral process and has been examined extensively in the US and other countries, yet there has been little attention to the patient's perspective of the information transfer process. This cross-sectional study examined the quality of the information received by patients with a chronic condition from the referring and specialist physician in the specialist referral process and the relationship of the quality of information received to trust in the physicians.

Methods: Structured telephone interviews were conducted with a random sample of 250 patients who had experienced a referral to a specialist for the first visit for a chronic condition within the prior six months.

The NAD biosynthesis inhibitor APO866 has potent antitumor activity against hematologic malignancies.

APO866 inhibits nicotinamide phosphoribosyltransferase (NMPRTase), a key enzyme involved in nicotinamide adenine dinucleotide (NAD) biosynthesis from the natural precursor nicotinamide. Intracellular NAD is essential for cell survival, and NAD depletion resulting from APO866 treatment elicits tumor cell death. Here, we determine the in vitro and in vivo sensitivities of hematologic cancer cells to APO866 using a panel of cell lines (n = 45) and primary cells (n = 32).

A statewide assessment of e-HIT use by all healthcare providers.

Knowledge of capacity and use of health information technology is essential in developing a secure interoperable statewide electronic health network. The purpose of this research was to conduct a comprehensive state-wide assessment of multiple healthcare providers and translate the data through geospatial mapping into a model to guide the development of RHIOs and HIEs. This research reflects the most comprehensive e-Health adoption survey to date for state healthcare decision makers in the extant literature.

Blood vessel maturation and response to vascular-disrupting therapy in single vascular endothelial growth factor-A isoform-producing tumors.

Tubulin-binding vascular-disrupting agents (VDA) are currently in clinical trials for cancer therapy but the factors that influence tumor susceptibility to these agents are poorly understood. We evaluated the consequences of modifying tumor vascular morphology and function on vascular and therapeutic response to combretastatin-A4 3-O-phosphate (CA-4-P), which was chosen as a model VDA. Mouse fibrosarcoma cell lines that are capable of expressing all vascular endothelial growth factor (VEGF) isoforms (control) or only single isoforms of VEGF (VEGF120, VEGF164, or VEGF188) were developed under endogenous VEGF promoter control.

Defining elements of success: a critical pathway of coalition development.

In recent decades, coalitions have been established to address many public health problems, including injury prevention. A partnership among the Kentucky Injury Prevention and Research Center and four injury prevention coalitions has documented the developmental stages of successful coalitions. This developmental process was constructed through the analysis of participating coalition documents, such as each coalition's mission statement, bylaws or rules of operation, the use of committees within the organization, frequency of meetings, and additional historical documents.

The use of photovoice as a method of facilitating deliberation.

Efforts have been made in one rural Appalachian county to broaden local participation in a community health assessment. Through a series of community forums and a photovoice project, residents named community health needs and assets, framed potential solutions, and selected possible action steps to improve the local health status. Photographs and narratives from the photovoice project supplemented information from preliminary health forums to devise a framework of possible solutions to the identified health problems.

Patient safety in after-hours telephone medicine.

Objectives: This study analyzed our family medicine department's after-hours telephone medicine systems at an academic health center from a patient safety perspective. The research questions were (1) What are the threats to patient safety associated with after-hours telephone medicine and (2) What kinds of errors are made during after-hours telephone medicine?

Methods: Subjects were patients at the University of Kentucky family medicine practice who called in to the after-hours answering service. Telephone interviews were conducted with 64 patients over 10 weeks.

Discovery and development of anticancer aptamers.

Aptamers, also termed as decoys or "chemical antibodies," represent an emerging class of therapeutics. They are short DNA or RNA oligonucleotides or peptides that assume a specific and stable three-dimensional shape in vivo, thereby providing specific tight binding to protein targets. In some cases and as opposed to antisense oligonucleotides, effects can be mediated against extracellular targets, thereby preventing a need for intracellular transportation.

The role of 17beta-hydroxysteroid dehydrogenases in modulating the activity of 2-methoxyestradiol in breast cancer cells.

The bis-sulfamoylated derivative of 2-methoxyestradiol (2-MeOE2), 2-methoxyestradiol-3,17-O,O-bis-sulfamate (2-MeOE2bisMATE), has shown potent antiproliferative and antiangiogenic activity in vitro and inhibits tumor growth in vivo. 2-MeOE2bisMATE is bioavailable, in contrast to 2-MeOE2 that has poor bioavailability. In this study, we have examined the role of 17beta-hydroxysteroid dehydrogenase (17beta-HSD) type 2 in the metabolism of 2-MeOE2.

The public and public health organizations: issues for community engagement in public health.

Deliberative processes are beginning to take effect in the public health sector. Public health organizations have a critical role in fostering local deliberation during the planning and implementation of community health efforts. The chief executive officer (CEO) of eight national public health constituent organizations were provided background readings about deliberation and its potential role in community public health planning.

Information-seeking behaviors of practitioners in a primary care practice-based research network (PBRN).

Objective: The aim of this study was to examine the information-seeking behaviors (e.g., information resource usage patterns, access to types of sources and to medical libraries, and use of particular information technologies) of members in a primary care practice-based research network (PBRN) to inform future efforts supporting primary care practitioners in their daily care of patients.

Increasing awareness of health care resources for the uninsured and underinsured:a pilot study.

Programs are available to provide assistance to the uninsured, but information about how to access those programs is not readily available to the average uninsured citizen. A pilot study involving the University of Kentucky Family and Consumer Science Agents and Homemaker groups in two rural counties significantly increased the number of people who accessed one of the programs, Health Kentucky. Findings from the study could be validated in other Kentucky counties and with other types of health-related messages.

Pharmacokinetics of the nonsteroidal steroid sulphatase inhibitor 667 COUMATE and its sequestration into red blood cells in rats.

Breast cancer is a major cause of mortality in Western countries and there is an urgent requirement for novel treatment strategies. The nonsteroidal sulphatase inhibitor 667 COUMATE inhibits hepatic steroid sulphatase and growth of oestrone sulphate stimulated tumours in the nitrosomethylurea-induced rat mammary model. Other compounds that contain an aryl sulphamate moiety, for example, oestrone-3-O-sulphamate, are sequestered into red blood cells (RBCs).

The voice of the public in public health policy and planning: the role of public judgment.

Community involvement with public health planning and implementation are vital to improving community health. There are a variety of community health models that are available. We describe these four models from the perspective of how they involve the broader community.

Public health competencies required by managed care organizations.

The authors developed a list of population-based public health competencies. They surveyed the chief executive officer, chief medical officer, and chief quality control person at a randomly selected group of managed care organizations drawn from the membership of the American Association of Health Plans. The authors asked them to rank those competencies that were essential for them in their work with their organization.

Current state of information technology use in a US primary care practice-based research network.

Objectives: To examine the current levels of information technology (IT) use in a primary care practice-based research network (PBRN) in order to inform future development of its infrastructure.

Participants: Every primary care practitioner who is a member of the Kentucky Ambulatory Network (KAN),as well as the office managers of each practice. Practitioners included family practitioners, general practitioners, nurse practitioners and physician assistants.

Pharmacokinetics and efficacy of 2-methoxyoestradiol and 2-methoxyoestradiol-bis-sulphamate in vivo in rodents.

2-Methoxyoestradiol (2-MeOE2) is an endogenous oestrogen metabolite that inhibits the proliferation of cancer cells in vitro, and it is also antiangiogenic. In vivo 2-MeOE2, when administered at relatively high doses, inhibits the growth of tumours derived from breast cancer cells, sarcomas and melanomas. Sulphamoylated derivatives of 2-MeOE2 are more potent inhibitors of in vitro breast cancer cell growth than 2-MeOE2.