克服肿瘤干细胞耐药性的策略和思路

肿瘤干细胞（cancersterncells,CSCs）是肿瘤细胞的祖细胞。已有的研究表明,肿瘤干细胞对多种化疗药物具有耐药性,是导致肿瘤治疗后复发的根源。研究针对肿瘤干细胞的治疗方法,克服肿瘤干细胞耐药性,将给肿瘤治疗模式带来全新的改变,有望彻底改善肿瘤患者的预后。     

Eating disorder NOS (EDNOS): an example of the troublesome "not otherwise specified" (NOS) category in DSM-IV

The “Not Otherwise Specified” (NOS) category within DSM-IV is designed for disorders of clinical severity that are not specified within broad diagnostic classes. “NOS” diagnoses are intended to be residual categories and they tend to be neglected by researchers. This can be inappropriate. The problems associated with certain NOS diagnoses are well illustrated by “Eating Disorder NOS” (sometimes termed EDNOS), which is the most common category of eating disorder encountered in routine clinical practice yet it has barely been studied. Indeed, there has been no research on its treatment. Interim and longer-term conceptual and practical solutions to the anomalous status of eating disorder NOS are proposed including the creation of a new diagnosis termed “mixed eating disorder”. Several of these solutions are of relevance to NOS categories in general. All the solutions should fulfil criteria for clinical utility.     

在西方医药审判中的一个亮点--科学哲学

科学证据不仅在司法审判中起着极其重要的作用,而且在科研成果的评价中也是不可取代的,但是在审判和科研成果评估中,对“科学是什么”这样一个更深层次的问题－科学哲学问题,历来没有得到应有的重视,通过美国止吐药本涤汀前后历时20年的审判历程,突出科学哲学在医药审判实践中的地位。     

Paradoxical drug response and the placebo effect: a discussion of Grunbaum's definitional scheme

Grunbaum claims that the remedial failure of atreatment's characteristic factors is thegeneric, objective property of a placebo. Hestipulates that a treatment is placebic if thisremedial failure exacerbates the targetdisorder. This stipulation can subsume asplacebic effects that might be solelypharmacological, e.g., paradoxical reactions tocertain psychiatric drugs. If that exacerbationcan be explained pharmacologically, then wemight question whether Grunbaum's definitionalscheme captures the core identity of what weusually intend by the placebo concept. Ipropose that this core identity is bestcaptured by a symbolic meaning hypothesis inwhich psychological factors exert thedeterminative influence.     

Drug discrimination using a conditioned taste-aversion paradigm in rhesus monkeys.

The development of drug discrimination was assessed in rhesus monkeys using the conditioned taste-aversion paradigm. Monkeys were initially trained to respond under a fixed-ratio 30-response schedule of food-pellet delivery to assess the rate-decreasing effects of alprazolam (0.03 to 3 mg/kg, i.m., 60 min presession). Alprazolam decreased responding at doses greater than 0.1 mg/kg. Discriminative stimulus effects of alprazolam were then assessed by giving 0.03 mg/kg before sessions in which 1.8 mEq/kg lithium chloride was given immediately after the session (alprazolam/lithium session). On intervening days, saline was given before and after the session (saline/saline session). Rates of responding decreased over successive alprazolam/lithium sessions and also during the saline/saline session that immediately followed an alprazolam/lithium session. During subsequent saline/saline sessions, rates of responding returned to levels near baseline rates within two to four sessions. The discriminative stimulus effects of alprazolam were then assessed by giving 0.1 mg/kg before sessions in which 1 mg/kg d-amphetamine was given immediately after the session (alprazolam/d-amphetamine session). Rates of responding decreased during subsequent alprazolam/d-amphetamine sessions in drug-experienced monkeys, but did not decrease during intervening saline/saline sessions. These findings demonstrate that drug stimuli associated with postsession drug injections can rapidly develop control over behavior and suggest that similar methods be explored in the assessment of drug discrimination.     

Matching under nonindependent variable-ratio schedules of drug reinforcement.

Response-contingent deliveries of oral pentobarbital maintained responding of 3 rhesus monkeys during daily 3-hr sessions. Deliveries of pentobarbital were arranged under nonindependent concurrent variable-ratio variable-ratio schedules. Responses to either schedule counted toward completion of both variable-ratio schedule requirements. This schedule is similar in some respects to conventional concurrent variable-interval variable-interval schedules, in which passage of time counts toward completion of the interval value on both schedules. Restricted nonindependent concurrent variable-ratio variable-ratio schedules were also studied. On that schedule, when a drug delivery was assigned to one spout, it had to be collected before responses on the opposite spout again counted toward completion of the schedule requirements. Relative reinforcer magnitude was varied by changing the drug concentration on one schedule while keeping the drug concentration constant on the other variable-ratio schedule. Under both types of concurrent variable-ratio schedules, the relative rate of responding corresponded to the relative drug intake. Unlike earlier studies of concurrent variable-interval variable-interval intravenous cocaine reinforcement, preference was proportionate to concentration, and exclusive preferences did not develop. The relationship between relative rate of responding and relative drug intake was well described by the generalized matching law.     

不确定性风险选择的抱负水平—相对效用整合理论

本文认为不确定性风险决策备择方案的选择标准既不是规范效用理论所主张的效用最大化,也不只是研究者们基于西蒙有限理性决策理论而提出的抱负水平,而是存在于决策不同阶段上的、由启发式策略控制着的这两种标准的整合,我们称之为抱负水平－相对效用整合标准。为此,我们在研究抱负水平结构的基础上提出了负险选择的抱负水平－相对效用整合理论及其支持性研究证据,并就有关问题进行了讨论与思考。指出抱负水平－相对效用整合是风     

THE UTILITY OF CURRICULUM-BASED MEASUREMENT FOR EVALUATING THE EFFECTS OF METHYLPHENIDATE ON ACADEMIC PERFORMANCE

Two case studies were conducted to investigate the utility of curriculum-based measurement of math and reading for evaluating the effects of methylphenidate on the academic performance of 2 students diagnosed with attention deficit hyperactivity disorder. Following baseline measurement, double-blind placebo-controlled procedures were employed to evaluate each student's response to three levels (5 mg, 10 mg, and 15 mg) of the medication. Results of the first study suggest that the curriculum-based measures were sensitive indicators of the student's response to medication. This finding was replicated in the second study. In the second study, when the student's follow-up dose of medication was based on trial-phase data, follow-up performance was improved compared to baseline performance. These case studies suggest that further research is warranted on the utility of curriculum-based measurements for monitoring and evaluating stimulant medication interventions with children with this disorder.     

Effects of delta 9-THC on marijuana smoking, dose choice, and verbal report of drug liking.

The effects of delta 9-tetrahydrocannabinol content of marijuana on cigarette smoking, dose choice, and verbal report of drug "liking" by adult males living in a residential laboratory were investigated. Marijuana cigarettes were available during programmed intervals while subjects were engaged in recreational activities. The tetrahydrocannabinol content of the cigarettes remained constant each day, but was changed across days. Subjects provided written ratings of drug liking at the end of each day. In the first study, placebo or active (2.3% delta 9-tetrahydrocannabinol) marijuana cigarettes were available for 1-, 2-, or 3-day intervals at varying times of day. The number of cigarettes smoked was unrelated to tetrahydrocannabinol content, although verbal reports of drug liking were consistently higher when marijuana cigarettes containing tetrahydrocannabinol were smoked. In a second study, a choice procedure, consisting of four 3-day blocks of 2 sample days and 1 choice day, was used. On sampling days, subjects smoked cigarettes varying in tetrahydrocannabinol content (0.0, 2.0, and 3.5%, w/w); on choice days they were allowed to choose between the two previously sampled doses. The number of cigarettes was not consistently related to tetrahydrocannabinol content. Ratings of drug liking were increased when marijuana cigarettes contained tetrahydrocannabinol, but ratings of marijuana containing 2.0% and 3.5% of the compound were similar. In contrast, subjects consistently chose the 3.5% dose over either the 0.0% or 2.0% dose. Dose choice was more sensitive to tetrahydrocannabinol content than either reports of drug liking or numbers of cigarettes smoked.     

Effects of income on drug choice in humans.

The effects of income (money available to spend during the experimental session) on human choice were examined in a concurrent-schedule arrangement. Subjects were 7 nicotine-dependent smokers, and reinforcers were puffs on the subject's usual brand of cigarette ("own") and puffs on a less preferred brand of cigarette with equal nicotine content ("other"). Across sessions, income varied and the price of the two reinforcers was held constant, with the other puffs one fifth the price of the own puffs. As income increased, consumption of own puffs increased while consumption of the less expensive other puffs decreased. These effects of income on choice were highly consistent across subjects. For some subjects, however, income had little effect on total puff consumption. Finally, an additional condition examined whether price and income manipulations would have functionally equivalent effects on choice by repeating an income condition in which the price of the other brand was increased. Although the increased price of the other puffs decreased their consumption in 4 subjects, 2 subjects showed increased consumption of the other puffs at the higher price. The results, when defined in economic terms, indicate that the own puffs were a normal good (consumption and income are directly related), the other puffs were an inferior good (consumption and income are inversely related), and the direct relationship between consumption of the other puffs and their price is defined as a Giffengood effect. The latter result also suggests that for these 2 subjects, price and income manipulations had equivalent effects on choice. These results extend findings from previous studies that have examined the effects of income on choice responding to human subjects and drug reinforcers, and provide a framework for further experimental tests of the effects of income on human choice behavior. Methodological and theoretical implications for the study of choice and for behavioral pharmacology are discussed.