ABSTRACT
ABSTRACT: Sleep is critical to a person's physiological and psychological functioning. Approximately 30% to 40% of the general population experiences insomnia, and among patients with mental health conditions, the prevalence of insomnia and other sleep disturbances rises to about 70%. Insomnia is associated with many adverse health issues, including lower immunity, weight gain, elevated BP, and increased mortality, and it is often undiagnosed and either untreated or self-treated. Providers can work together with patients to enact measures-such as implementation of enhanced sleep hygiene, engagement in cognitive behavioral therapy, and treatment of any underlying causes-that can markedly improve patient sleep quality. This article provides an overview of evidence-based best practices and whole-person strategies that NPs can adopt to address poor sleep quality in adult patients, and it serves as a primer for primary care NPs on common presentations of several sleep disorders.
Subject(s)
Sleep Quality , Humans , Adult , Nurse Practitioners , Sleep Initiation and Maintenance Disorders/nursing , Sleep Initiation and Maintenance Disorders/therapy , Cognitive Behavioral Therapy , Sleep Wake Disorders/epidemiology , Practice Guidelines as Topic , Sleep HygieneABSTRACT
BACKGROUND: Hepatocellular carcinoma (HCC) commonly presents at a late stage when surgery is no longer a curative option. As such, novel therapies for advanced HCC are needed. Oncolytic viruses are a viable option for cancer therapy owing to their ability to specifically infect, replicate within, and kill cancer cells. In this study, we have investigated the ability of GLV-2b372, a novel light-emitting recombinant vaccinia virus derived from a wild-type Lister strain, to kill HCC. METHODS: Four human HCC cell lines were assayed in vitro for infectivity and cytotoxicity. Viral replication was quantified via standard viral plaque assays. Flank HCC xenografts generated in athymic nude mice were treated with intratumoral GLV-2b372 to assess for tumor growth inhibition and viral biodistribution. RESULTS: Infectivity occurred in a time- and concentration-dependent manner with 70% cell death in all cell lines by day 5. All cell lines supported efficient viral replication. At 25 days after infection, flank tumor volumes decreased by 50% whereas controls increased by 400%. Tumor tissue demonstrated substantial GLV-2b372 infection at 24 hours, 48 hours, and 2 weeks. CONCLUSION: We demonstrate that GLV-2b372 efficiently kills human HCC in vitro and in vivo and is a viable treatment option for patients with HCC.
Subject(s)
Carcinoma, Hepatocellular/therapy , Genetic Therapy , Liver Neoplasms/therapy , Oncolytic Virotherapy , Oncolytic Viruses/genetics , Vaccinia virus/genetics , Animals , Cell Line, Tumor , Female , Humans , Mice , Mice, Nude , Treatment Outcome , Xenograft Model Antitumor AssaysABSTRACT
BACKGROUND: Sorafenib is the standard systemic therapy for unresectable or recurrent hepatocellular carcinoma (HCC) but adds minimal increase in survival. Therefore, there is a great need to develop novel therapies for advanced or recurrent HCC. One emerging field of cancer treatment involves oncolytic viruses that specifically infect, replicate within, and kill cancer cells. In this study, we examined the ability of GLV-1h68, a recombinant vaccinia virus derived from the vaccine strain that was used to eradicate smallpox, to kill sorafenib-resistant (SR) HCC cell lines. METHODS: Four SR HCC cell lines were generated by repeated passage in the presence of sorafenib. Median inhibitory concentration was determined for all cell lines. The infectivity, viral replication, and cytotoxicity of GLV-1h68 were assayed for both parental and SR HCC cells. RESULTS: Infectivity increased in a time and concentration-dependent manner in all cell lines. All cell lines supported efficient replication of virus. No difference between the rates of cell death between the parental and SR cell lines was observed. CONCLUSION: Our results demonstrate that the oncolytic vaccinia virus GLV-1h68 kills both parental and SR HCC cell lines efficiently. This study indicates that patients who have failed treatment with sorafenib remain viable candidates for oncolytic therapy.
Subject(s)
Antineoplastic Agents/pharmacology , Carcinoma, Hepatocellular/therapy , Liver Neoplasms/therapy , Niacinamide/analogs & derivatives , Oncolytic Virotherapy/methods , Phenylurea Compounds/pharmacology , Vaccinia virus/genetics , Vaccinia virus/immunology , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Cell Death/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Drug Resistance, Neoplasm , Genetic Engineering , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Niacinamide/pharmacology , Sorafenib , Vaccinia virus/physiology , Viral Plaque Assay , Virus ReplicationABSTRACT
The development of targeted agents and chemotherapies for pancreatic cancer has only modestly affected clinical outcome and not changed 5-year survival. Fortunately the genetic and molecular mechanisms underlying pancreatic cancer are being rapidly uncovered and are providing opportunities for novel targeted therapies. Oncolytic viral therapy is one of the most promising targeted agents for pancreatic cancer. This review will look at the current state of the development of these self-replicating nanoparticles in the treatment of pancreatic cancer.