Carrier cell-mediated cell lysis of squamous cell carcinoma by squamous cell carcinoma antigen 1 promoter-driven oncolytic adenovirus

The squamous cell carcinoma antigen (SCCA) serves as a serological marker for squamous cell carcinomas. Molecular cloning of the SCCA genomic region has revealed the presence of two tandemly arrayed genes, SCCA1 and SCCA2. We examined the promoter activity of the 5'-flanking proximal region of the SCCA1 gene. Deletion analysis of SCCA1 promoter identified a 175-bp core promoter region and an enhancer region at -525 to -475 bp upstream of the transcription start site. The transcriptional activity of the SCCA1 promoter was up-regulated in squamous cell carcinoma cells, compared with normal keratinocyte, normal non-keratinocyte and adenocarcinoma cells. Five tandem repeats of enhancer increased SCCA1 promoter activity by 4-fold. Oncolytic adenovirus driven by the SCCA1 promoter with 5 tandem repeats of enhancer specifically killed squamous cell carcinoma cells in vitro and in vivo. A549 carrier cells infected with the oncolytic adenovirus induced complete regression of tumor by overcoming immunogenicity and adenovirus-mGM-CSF augmented the antitumor effect of carrier cells. These findings suggest that SCCA1 promoter is a potential target of gene therapy for squamous cell carcinoma

Identifying cognitive dysfunction using the nurses’ rapidly clinical judgment in elderly inpatients

: The aim of this study was to examine the relationship between nurses’ clinical judgment on cognitive function by fall risk assessment and mini-mental state examination (MMSE) scores in elderly inpatients. : We studied 61 consecutive hospitalized patients who received both comprehensive geriatric assessment (CGA) and fall risk assessment at the Department of Geriatric Medicine in Kyoto University Hospital from January 2006 to June 2010. During the fall risk assessment at admission, primary nurses evaluated the cognitive function by four items (with or without disorientation, impaired judgment, lack of comprehension, and memory loss), while a trained clinical assistant performed CGA including MMSE. Patients were divided into three groups according to the MMSE scores. The association between the four items of judgment by nurses and MMSE scores was then studied. : The mean age was 80.1 years and 55.7% of the patients were female. The percentage of patients judged to have impaired judgment, lack of comprehension, and memory loss was higher in patients with lower MMSE scores (impaired judgment, p for trend = 0.001; lack of comprehension, p for trend = 0.043; memory loss, p for trend = 0.001). The percentage of patients judged to have at least one of the four abnormalities was also significantly higher in patients with lower MMSE scores (p for trend : These data indicate that a comprehensive evaluation using all the four items on cognitive impairment is more effective in detecting cognitive impairment in elderly than using individual items, although one-third of cognitively impaired elderly patients may miss detection despite the use of the four items. Better approaches should be developed to identify cognitively impaired elderly patients by nurses

Long-Term Survival of a Patient with Invasive Signet-Ring Cell Carcinoma of the Urinary Bladder Managed by Combined S-1 and Cisplatin Adjuvant Chemotherapy

Primary signet-ring cell carcinoma of the urinary bladder is extremely rare and patient survival is very poor. The disease usually presents at advanced stages because the cancer progresses rapidly. The only option for effective treatment is radical cystectomy, and no effective chemotherapy has been established for this variant. We report a case of signet-ring cell carcinoma of the urinary bladder with a long-term survival of 90 months owing to radical cystectomy and combination adjuvant chemotherapy with S-1 and cisplatin. To our knowledge, this is the first report to demonstrate the long-term therapeutic activity of combination S-1 and cisplatin adjuvant chemotherapy against invasive signet-ring cell carcinoma of the urinary bladder