Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.3.1.51 (HDR)
 605 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Well-known radiotherapeutic strategies for hypoxic cells include hypoxic radiosensitizers, heavy particles, and fractionated irradiation. This study attempted to obtain the ultimate effectiveness of these strategies by combining nicotinamide plus carbogen (N + C) as a hypoxic radiosensitizer with fractionated pions. In addition, the influence on the N + C effect of X-ray dose rate used as a reference radiation was evaluated. When SCCVII tumors in the dorsum of feet reached 50 mm3 in volume, they were irradiated with pions (0.2 Gy/min), the same dose rate (LDR; 0.2 Gy/min) X-rays, or high dose rate (HDR; 1.5 Gy/min) X-rays in 10 fractions over 11 days. Nicotinamide (0.5 mg/g) was administered i.p. one hour before irradiation, and normobaric carbogen (95% oxygen and 5% carbon dioxide) was breathed from 10 min before irradiation. The effect was evaluated by tumor growth time (TGT50) assay. The combination of N + C significantly enhanced the effect of 30 Gy LDR and 28 Gy HDR X-rays, with the effect corresponding to that of 39 Gy HDR X-rays: the enhancement ratios were 1.2 and 1.4, respectively. The effect of 20 Gy pions was equivalent to the effect of 33 Gy HDR X-rays (ratio of 1.65), or the effect of N + C combined with 28 Gy HDR X-rays. However, N + C did not enhance the effect of 20 Gy pions. This suggested that the fractionated pions had great biological effectiveness against hypoxic cells. In conclusion, N + C afforded no additional benefit with fractionated pions, but it was thought to be of value for fractionated X-rays, even in a dose rate of 0.2 Gy/min.
 ...
PMID:Radiosensitizing effect of nicotinamide and carbogen combined in fractionated pions or x-rays in SCCVII tumors. 885 Mar 70

Clinical modulation of radiosensitivity via combined fractionated high dose rate and continuous ultra-low dose rate irradiation (ULDR) holds promise for the radiosensitization of human malignant gliomas. We measured both the in vitro and in vivo responses of a human malignant glioma cell line to combined continuous ULDR and high dose rate treatments. For in vitro ULDR treatments, U251 human malignant glioma cells were cultured in media containing tritiated water to yield a continuous dose rate of 0.03 Gy/hr. After exposures of 24, 48, or 72 hr, cells were acutely (1.1 Gy/min) irradiated, replated, and scored for colony formation. In vivo, U251 flank xenografts in nude mice had 125-iodine (125-I) seed brachytherapy at a dose rate of 0.05 Gy/hr. For whole-body continuous ULDR (0.03 Gy/hr), a 137-Cs source was mounted a fixed distance above the cages of animals bearing xenografts. After 3 days' continuous exposure, xenografts were acutely irradiated (2 Gy x 8 vs. 5 Gy x 2 daily fractions), and the regrowth delay in tumors was measured. In vitro, exposure to ULDR (0.03 Gy/hr) alone caused only modest killing and reduced the surviving fraction by approximately 0.2 logs after 72 hr exposure. The highest (10 Gy) dose of acute irradiation alone reduced survival by 1 log. However, U251 cell killing increased to 2.5 logs after combined HDR and ULDR treatments. Linear-quadratic modeling showed comparatively greater increase in the beta than the alpha coefficients of the linear-quadratic model for cell killing. In vivo, the 125-I seed brachytherapy treatments delayed tumor growth but resulted in no regression. The HDR treatments (5 Gy x 2 or 2 Gy x 8 daily fractions) caused growth delays (in days) of 17+/-2 or 16+/-2 (P=NS) days, respectively. The combined seed and 5 Gy x 2 or 2 Gy x 8 daily fractions regimen resulted in striking prolongation of regrowth delay (52.3+/-8.7 vs. 59.5+/-7.7 days) (P < 0.001 vs. HDR treatments alone). External ULDR alone caused no regression and minimal growth delay. Combined continuous external ULDR and the 5 Gy x 2 vs. 2 Gy x 8 daily fraction regimens resulted in prolongation of growth delay (33+/-0.9 (P=0.01 vs. 5 Gy x 2 daily fractions alone) vs. 35+/-0.7 (P=0.049 vs. 2 Gy x 8 daily fractions alone). We conclude that continuous ULDR increases the effect of HDR treatments of experimental malignant glioma. This increased effect may prove clinically important in the treatment of human malignant brain tumors.
 ...
PMID:Protracted exposure radiosensitization of experimental human malignant glioma. 988 41