Efficient Prodrug Activator Gene Therapy by Retroviral Replicating Vectors Prolongs Survival in an Immune-Competent Intracerebral Glioma Model.

Prodrug activator gene therapy mediated by murine leukemia virus (MLV)-based retroviral replicating vectors (RRV) was previously shown to be highly effective in killing glioma cells both in culture and in vivo. To avoid receptor interference and enable dual vector co-infection with MLV-RRV, we have developed another RRV based on gibbon ape leukemia virus (GALV) that also shows robust replicative spread in a wide variety of tumor cells. We evaluated the potential of GALV-based RRV as a cancer therapeutic agent by incorporating yeast cytosine deaminase (CD) and E. coli nitroreductase (NTR) prodrug activator genes into the vector. The expression of CD and NTR genes from GALV-RRV achieved highly efficient delivery of these prodrug activator genes to RG-2 glioma cells, resulting in enhanced cytotoxicity after administering their respective prodrugs 5-fluorocytosine and CB1954 in vitro. In an immune-competent intracerebral RG-2 glioma model, GALV-mediated CD and NTR gene therapy both significantly suppressed tumor growth with CB1954 administration after a single injection of vector supernatant. However, NTR showed greater potency than CD, with control animals receiving GALV-NTR vector alone (i.e., without CB1954 prodrug) showing extensive tumor growth with a median survival time of 17.5 days, while animals receiving GALV-NTR and CB1954 showed significantly prolonged survival with a median survival time of 30 days. In conclusion, GALV-RRV enabled high-efficiency gene transfer and persistent expression of NTR, resulting in efficient cell killing, suppression of tumor growth, and prolonged survival upon CB1954 administration. This validates the use of therapeutic strategies employing this prodrug activator gene to arm GALV-RRV, and opens the door to the possibility of future combination gene therapy with CD-armed MLV-RRV, as the latter vector is currently being evaluated in clinical trials.

Care Needs of Community-Residing Male Patients with Vascular Cognitive Impairment.

PURPOSE: The aim of this study was to identify the care needs of male patients with vascular cognitive impairment (VCI) and their caregivers. PATIENTS AND METHODS: This cross-sectional study enrolled 389 male patients with VCI and their caregivers who were cared for by the dementia collaborative care team at Changhua Christian Hospital, Taiwan. Fifteen care needs consisting of most of quality measures for people living with dementia and their caregivers were developed by the care team. Through face-to-face evaluations, individualized care needs were collected. The Apriori algorithm was used to identify care bundles for the patients and their caregivers. RESULTS: Six basic care needs for patients and their caregivers were identified, including appropriate schedule of activities, regular outpatient follow-up treatment, introduction and referral of social resources, referral to family support groups and care skills training, care for the mood of the caregiver, and health education for dementia and behavioral and psychological symptoms of dementia. Compared to subjects with all dementia subtypes from the previous studies, care for the mood of the caregiver was an important and frequent care need for the male patients with VCI and their caregivers. A comparison among the study and similar studies was made to highlight the strength of this study concentrating on the precise selection of care needs. CONCLUSION: Collaborative dementia care teams should monitor for caregivers' depression and include this care need into the care bundle when assessing male subjects with VCI.