In cancer gene therapy, restriction of antitumor transgene expression in a radiation field by use of ionizing radiation-inducible promoters is one of the promising approaches for tumor-specific gene delivery. Although tumor suppressor protein p53 is induced by low doses (<1 Gy) of radiation, there have been only a few reports indicating potential utilization of a p53-target gene promoter, such as that of the p21 gene. This is mainly because the transiently transfected promoter of p53-target genes is not much sensitive to radiation. We examined the response of the p21 gene promoter to low-dose radiation when transduced into a human breast cancer cell line MCF-7 by use of recombinant adeno-associated virus (rAAV) vectors. It was shown that the p21 gene promoter transduced by rAAV vectors was more highly radiation-responsive than that transiently transfected by electroporation. A significant induction of the p21 gene promoter by radiation of low doses down to 0.2 Gy was observed. When cells were transduced with the p21 gene promoter-driven HSVtk gene by rAAV vector, they were significantly sensitized to repetitive treatment with low dose radiation (1 Gy) in the presence of the prodrug ganciclovir. It was therefore considered that the p21 gene promoter in combination with a rAAV vector is potentially usable for the development of a low-dose radiation-inducible vector for cancer gene therapy.
X-Rays ; Tumor Cells, Cultured ; Transgenes/*radiation effects ; Transduction, Genetic ; Promoter Regions (Genetics)/*radiation effects ; Humans ; Genetic Vectors/*radiation effects ; Gene Therapy/methods ; Electroporation/methods ; Dose-Response Relationship, Radiation ; Cyclin-Dependent Kinase Inhibitor p21/*genetics ; Adenoviridae ; 3' Untranslated Regions/physiology

INTRODUCTIONPulse oximetry (SpO2) measures oxygen saturation but not alveolar ventilation. Its failure to detect alveolar hypoventilation during sedated endoscopy under oxygen supplementation has been reported. The aim of this study was to measure the masking effect of oxygen supplementation in SpO2 when alveolar hypoventilation develops during sedated endoscopy.

METHODSA total of 70 patients undergoing sedated diagnostic colonoscopy were randomly divided into two groups - oxygen supplementation group (n = 35) and room air breathing group (n = 35). SpO2 and end-tidal carbon dioxide (etCO2) were measured by non-intubated capnography during the procedure for all the patients.

RESULTSThe rise of etCO2 caused by alveolar hypoventilation was comparable in the two groups after sedation. SpO2 was significantly higher in the oxygen supplementation group than in the room air breathing group (98.6% ± 1.4% vs. 93.1% ± 2.9%; p < 0.001) at peak etCO2, and oxygen supplementation caused SpO2 to be overestimated by greater than 5% when compared with room air. SpO2 at peak etCO2 was reduced from the baseline before sedation for the oxygen supplementation and room air breathing groups by 0.5% ± 1.1% and 4.1% ± 3.1%, respectively (p < 0.001).

CONCLUSIONSpO2 alone is not adequate for monitoring alveolar ventilation during sedated endoscopy under oxygen supplementation due to possible delays in detecting alveolar hypoventilation in patients. Even if SpO2 decreases by only 1% during the procedure and its level remains near 100%, physicians should consider the onset of severe alveolar hypoventilation, which requires immediate intervention.

Adult ; Aged ; Carbon Dioxide ; analysis ; Colonoscopy ; Conscious Sedation ; Endoscopy ; Female ; Humans ; Hypoventilation ; diagnosis ; Male ; Middle Aged ; Monitoring, Intraoperative ; methods ; Oximetry ; methods ; Oxygen ; administration & dosage ; Respiration, Artificial

Objective: Bile duct tumor thrombosis in hepatocellular carcinoma (HCC) is a relatively rare event with a poor prognosis. Furthermore, bile duct tumor thrombus in HCC may be misdiagnosed when only imaging modalities are used. The efficiency of peroral cholangioscopy (POCS) in evaluating bile duct lesions has been reported.Patients: We present three cases of HCC with bile duct strictures in which POCS was performed as a preoperative evaluation.Results: In these three cases, diagnosing whether the lesion was a bile duct tumor thrombus on CT and endoscopic retrograde cholangiopancreatography was difficult. We performed POCS in three cases and were able to diagnose the presence of bile duct tumor thrombus of HCC, including differentiation from extrinsic compression of the bile duct.Conclusion: POCS for HCC with bile duct features is useful for the preoperative diagnosis of bile duct tumor thrombus, especially in cases where the surgical procedure depends on the presence of bile duct tumor thrombus.