Impact of treatment efficacy on the prognostic value of glucocorticoid receptor levels in childhood acute lymphoblastic leukemia

Glucocorticoid receptor (GR) levels were quantitated in leukemic blasts from bone marrow aspirates of 249 children with acute lymphoblastic leukemia (ALL) who were entered on two St. Jude Total Therapy Studies. Of these, 235 were evaluable for analysis of the relation of GR levels to clinical outcome. For the 42 patients in the earlier Total Therapy Study IX, lower GR levels (<16,000 sites/cell) were associated with both induction failure and more frequent relapse (p <0.01) [Cancer Research, Vol. 42, p. 4801 (1982)]. When patients with ‘high-risk’ features (leukocyte count >100 × 10³/mm³, positive erythrocyte rosette test, central nervous system involvement, and mediastinal mass) were excluded, lower receptor levels were still associated with early and more frequent relapse (p <0.02). The other 193 evaluable patients were consecutively admitted to Total Therapy Study X, in which patients with ‘standard-risk’ or ‘high-risk’ features were assigned to separate protocols — XS and XH, respectively. Induction chemotherapy in both protocols consisted of prednisone, vincristine and l-asparaginase; patients in the XH protocol received additional epipodophyllotoxin (VM-26) and cytosine arabinoside twice a week for 2 weeks preceding the conventional induction therapy. To compare the prognostic value of GR level in Study X with that of Study IX (which included both ‘high-risk’ and ‘standard-risk’ patients but did not separate them into different protocol groups), children in the XH and XS protocols were analysed together. The proportion of patients with ‘standard-risk’ features was the same in the two studies: 69% in Study IX and 73% in Study X. In Study X, which had a significantly better treatment result (p <0.001), lower receptor levels were not associated with induction failure, but were correlated with more frequent relapse (p <0.05). When patients in XH and XS protocols were analysed separately, however, receptor levels were no longer related to treatment outcome. Thus, GR level in childhood ALL has prognostic value, but it is not an independent factor and its importance is related to the efficacy of treatment.     

Age-based refinement of referral criteria for photoscreening

OBJECTIVE: To evaluate examination results from preschool children referred from photoscreening, and to adjust referral criteria for suspected astigmatism. DESIGN: Cross-sectional study and noncomparative case series. PARTICIPANTS: Thirty-one thousand fifty-three preschool children. METHODS: Analysis of (1) referral rate and unreadable photograph rate for all children screened, (2) examination results and treatment plan for all children referred for suspected astigmatism, and (3) examination results and treatment for all referred children aged less than 1 year. MAIN OUTCOME MEASURES: Referral rate, unreadable photograph rate, predictive value positive, treatment plan. RESULTS: The referral rate dropped from 7.8% for children 6 to 11 months to 5.3% for all other ages. The unreadable photograph rate declined exponentially from 12.1% for children aged 6 to 11 months to 1.1% for children aged 4 years. The predictive value positive of a photoscreen referral for all children in the 6- to 11-month age group was 30%, and only 12 of the 94 referred children were treated. The predictive value positive for children less than 1 year of age referred with suspected astigmatism was even lower (25%), and only one child in this age group was treated. The predictive value positive increased with age, and a higher percentage of older children were treated. For children at least 3 years old referred for suspected astigmatism, the predictive value positive was 67% when the examination was performed by a pediatric ophthalmologist. Strabismus, anisometropia, and high hypermetropia were diagnosed in such patients age 2 and older but never in younger children. CONCLUSIONS: Children less than 1 year of age have a much lower pass rate from photoscreening than do older children because of a higher referral rate and higher unreadable rate in this age group. When these children are examined, significant pathosis is usually absent, and intervention is rarely initiated. Most children age 2 and older who are referred for suspected astigmatism have a high likelihood of significant pathosis. It is probably unnecessary to examine children less than age 2 when their photoscreening suggests only astigmatism; conversely, referrals should still be provided for these children when their screening suggests other potentially amblyogenic factors.     

Differential effects of chronic ethanol feeding on cytochrome P-448- and P-450-mediated drug metabolism in the rat

The effects of chronic ethanol feeding on cytochrome P-448- and P-450-mediated drug metabolism have been studied both in vivo and in vitro in the rat, using caffeine, phenacetin, antipyrine and aminopyrine as test substrates. N-Demethylation of aminopyrine (P-450 mediated) was increased both in vivo and in vitro in rats after chronic ethanol feeding (P < 0.05) whereas in vivoN-demethylation of caffeine and O-dealkylation of phenacetin (P-448 mediated) were unchanged in the same animals. N-rmDemethylation of antipyrine was increased by both phenobarbital and 3-methylcholanthrene pretreatment and by chronic ethanol feeding (P < 0.05), possibly due to cytochrome P-450 induction. Furthermore, the Michaelis affinity constants. K_m, for hepatic microsomal aminopyrine N-demethylase and antipyrine N-demethylase were lower in chronic ethanol-fed animals (P < 0.05), suggesting a qualitative change in the enzymes resulting in greater substrate affinity. These findings suggest a differential effect of chronic ethanol feeding on the induction of cytochrome P-450- and cytochrome P-448-mediated drug metabolism, with a greater effect on the former microsomal system.     

华蟾素胶囊联合TN化疗方案对中晚期宫颈癌放疗患者血清SCC、TSGF水平及生存质量的影响

目的:探讨华蟾素胶囊联合TN化疗方案(紫杉醇+奈达铂)在中晚期宫颈癌放疗患者中的应用效果。方法:选取中晚期宫颈癌放疗患者71例,按照随机数字表法分组,对照组35例给予TN化疗方案治疗,观察组36例给予TN化疗方案+华蟾素胶囊治疗,观察比较两组临床疗效及治疗前后血清鳞状细胞癌相关抗原（SCC）、肿瘤特异性生长因子（TSGF）水平及生存质量各维度评分变化情况,并统计两组毒副反应发生情况及1年、2年、3年生存率。结果:观察组临床缓解率为83.33%（30/36）,高于对照组57.14%（20/35）（P＜0.05）;治疗4个疗程后观察组血清SCC、TSGF水平低于对照组（P＜0.05）;观察组便秘、腹泻及恶心呕吐发生率与对照组比较,差异无统计学意义（P＞0.05）;观察组白细胞下降发生率为11.11%（4/36）,低于对照组31.43%（11/35）（P＜0.05）;治疗4个疗程后观察组认知、角色、躯体、社会及情绪功能生存质量评分高于对照组（P＜0.05）;观察组1年生存率为91.67%（33/36）、2年生存率为86.11%（31/36）、3年生存率为77.78%（28/36）,与对照组（91.43%、85.71%、74.29%）比较,差异无统计学意义（P＞0.05）。结论:TN化疗方案联合华蟾素胶囊可降低中晚期宫颈癌放疗患者血清TSGF、SCC水平,提高其生存质量,疗效确切,安全性高。     

The molecular basis for induction of human cancers by tobacco specific nitrosamines

Cellular DNA damage that is misrepaired or not repaired, constitutes a necessary, although not sufficient prerequisite for induction of cancer. For carcinogenic oral snuffs with extremely high concentrations of tobacco specific nitrosamines (TSNA) the DNA adduct levels predicted from animal experiments exceed those found in "unexposed" individuals. On the other hand, and supported by extensive Swedish epidemiological data, no significant increase of TSNA-induced DNA damages can be anticipated in humans from the use of low-nitrosamine oral snuffs. The extrapolated adduct concentrations are orders of magnitude lower than those found in the corresponding human tissues, a discrepancy that is difficult to account for by species differences. Furthermore, in exposed subjects the observed increment in the background levels of pyridyloxobutyl(POB)-hemoglobin adducts - a relevant indicator for TSNA activation - lie in a range predicted by rodent data. When based on the same type of tissues this provides justification for extrapolating rates of TSNA induced adduct formation from animals to humans. A TSNA exposure that does not affect the background level of pro-mutagenic DNA lesions should be considered as "virtually safe". The high background concentrations of methylated and POB-DNA adducts in "unexposed" humans must be ascribed to other sources than tobacco.