TRPV6 Determines the Effect of Vitamin D3 on Prostate Cancer Cell Growth

Despite remarkable advances in the therapy and prevention of prostate cancer it is still the second cause of death from cancer in industrialized countries. Many therapies initially shown to be beneficial for the patients were abandoned due to the high drug resistance and the evolution rate of the tumors. One of the prospective therapeutical agents even used in the first stage clinical trials, 1,25-dihydroxyvitamin D3, was shown to be either unpredictable or inefficient in many cases. We have already shown that TRPV6 calcium channel, which is the direct target of 1,25-dihydroxyvitamin D3 receptor, positively controls prostate cancer proliferation and apoptosis resistance (Lehen'kyi et al., Oncogene, 2007). However, how the known 1,25-dihydroxyvitamin D3 antiproliferative effects may be compatible with the upregulation of pro-oncogenic TRPV6 channel remains a mystery. Here we demonstrate that in low steroid conditions 1,25-dihydroxyvitamin D3 upregulates the expression of TRPV6, enchances the proliferation by increasing the number of cells entering into S-phase. We show that these pro-proliferative effects of 1,25-dihydroxyvitamin D3 are directly mediated via the overexpression of TRPV6 channel which increases calcium uptake into LNCaP cells. The apoptosis resistance of androgen-dependent LNCaP cells conferred by TRPV6 channel is drastically inversed when 1,25-dihydroxyvitamin D3 effects were combined with the successful TRPV6 knockdown. In addition, the use of androgen-deficient DU-145 and androgen-insensitive LNCaP C4-2 cell lines allowed to suggest that the ability of 1,25-dihydroxyvitamin D3 to induce the expression of TRPV6 channel is a crucial determinant of the success or failure of 1,25-dihydroxyvitamin D3-based therapies

Relapse prevention for addictive behaviors

The Relapse Prevention (RP) model has been a mainstay of addictions theory and treatment since its introduction three decades ago. This paper provides an overview and update of RP for addictive behaviors with a focus on developments over the last decade (2000-2010). Major treatment outcome studies and meta-analyses are summarized, as are selected empirical findings relevant to the tenets of the RP model. Notable advances in RP in the last decade include the introduction of a reformulated cognitive-behavioral model of relapse, the application of advanced statistical methods to model relapse in large randomized trials, and the development of mindfulness-based relapse prevention. We also review the emergent literature on genetic correlates of relapse following pharmacological and behavioral treatments. The continued influence of RP is evidenced by its integration in most cognitive-behavioral substance use interventions. However, the tendency to subsume RP within other treatment modalities has posed a barrier to systematic evaluation of the RP model. Overall, RP remains an influential cognitive-behavioral framework that can inform both theoretical and clinical approaches to understanding and facilitating behavior change

Quantifying Individual Variation in the Propensity to Attribute Incentive Salience to Reward Cues

If reward-associated cues acquire the properties of incentive stimuli they can come to powerfully control behavior, and potentially promote maladaptive behavior. Pavlovian incentive stimuli are defined as stimuli that have three fundamental properties: they are attractive, they are themselves desired, and they can spur instrumental actions. We have found, however, that there is considerable individual variation in the extent to which animals attribute Pavlovian incentive motivational properties (“incentive salience”) to reward cues. The purpose of this paper was to develop criteria for identifying and classifying individuals based on their propensity to attribute incentive salience to reward cues. To do this, we conducted a meta-analysis of a large sample of rats (N = 1,878) subjected to a classic Pavlovian conditioning procedure. We then used the propensity of animals to approach a cue predictive of reward (one index of the extent to which the cue was attributed with incentive salience), to characterize two behavioral phenotypes in this population: animals that approached the cue (“sign-trackers”) vs. others that approached the location of reward delivery (“goal-trackers”). This variation in Pavlovian approach behavior predicted other behavioral indices of the propensity to attribute incentive salience to reward cues. Thus, the procedures reported here should be useful for making comparisons across studies and for assessing individual variation in incentive salience attribution in small samples of the population, or even for classifying single animals

The CogBIAS longitudinal study protocol: cognitive and genetic factors influencing psychological functioning in adolescence.

BACKGROUND: Optimal psychological development is dependent upon a complex interplay between individual and situational factors. Investigating the development of these factors in adolescence will help to improve understanding of emotional vulnerability and resilience. The CogBIAS longitudinal study (CogBIAS-L-S) aims to combine cognitive and genetic approaches to investigate risk and protective factors associated with the development of mood and impulsivity-related outcomes in an adolescent sample. METHODS: CogBIAS-L-S is a three-wave longitudinal study of typically developing adolescents conducted over 4 years, with data collection at age 12, 14 and 16. At each wave participants will undergo multiple assessments including a range of selective cognitive processing tasks (e.g. attention bias, interpretation bias, memory bias) and psychological self-report measures (e.g. anxiety, depression, resilience). Saliva samples will also be collected at the baseline assessment for genetic analyses. Multilevel statistical analyses will be performed to investigate the developmental trajectory of cognitive biases on psychological functioning, as well as the influence of genetic moderation on these relationships. DISCUSSION: CogBIAS-L-S represents the first longitudinal study to assess multiple cognitive biases across adolescent development and the largest study of its kind to collect genetic data. It therefore provides a unique opportunity to understand how genes and the environment influence the development and maintenance of cognitive biases and provide insight into risk and protective factors that may be key targets for intervention.This work was supported by the European Research Council (ERC) under the European Union’s Seventh Framework Programme (FP7/2007–2013)/ERC grant agreement no: [324176]

The search for new ways to change implicit alcohol-related cognitions in heavy drinkers

Item does not contain fulltextThis article summarizes a symposium on new ways to change implicit alcohol-related cognitions, presented at the 2005 Annual Meeting of the Research Society on Alcoholism in Santa Barbara, California, organized by Wiers and Cox. During the past few years, research has demonstrated that implicit cognitions predict unique variance in prospective alcohol use and preliminary results indicate that they also predict treatment outcomes. The central question in this symposium was how implicit cognitions can be changed and how the changes will influence behavior. Field presented data showing that an attentional bias for alcohol can be altered by attentional training: heavy drinkers who were trained not to attend to alcohol stimuli reported less craving and drank less beer than those trained to attend to alcohol stimuli. Schoenmakers used a similar, clinically relevant attentional retraining (AR) procedure, heavy drinkers were trained not to attend to alcohol pictures or received no training. After the training, the AR group attended less to the alcohol pictures than the control group. Fadardi described the Alcohol Attentional Control Training Program (AACTP), which makes alcohol drinkers aware of the automatic, cognitive determinants of their drinking and aims to help them to gain control over these processes. Data were presented to support the effectiveness of the AACTP. Palfai presented data showing that alcohol drinkers can be taught to use implementation intentions to gain control over their drinking, which may be used to automatically activate self-control skills in the presence of alcohol cues. In his discussion, Stacy pointed out the importance of recent cognitive theories that integrate attention and memory processes—theories that can help us better understand the mechanisms involved in AR. Together, the studies presented demonstrate that there are promising new ways in which implicit alcohol-related cognitions and their effects on drinking can be changed. After further refinement, these procedures might be used in clinical interventions that have not previously addressed implicit cognitive processes.12 p

Changing implicit attitudes toward smoking: results from a web-based approach-avoidance practice intervention

Implicit attitudes have been shown to predict smoking behaviors. Therefore, an important goal is the development of interventions to change these attitudes. This study assessed the effects of a web-based intervention on implicit attitudes toward smoking and receptivity to smoking-related information. Smokers (N=284) were recruited to a two-session web-based study. In the first session, baseline data were collected. Session two contained the intervention, which consisted of assignment to the experimental or control version of an approach-avoidance task and assignment to an anti-smoking or control public service announcement (PSA), and post-intervention measures. Among smokers with less education and with plans to quit, implicit attitudes were more negative for those who completed the approach-avoidance task. Smokers with more education who viewed the anti-smoking PSA and completed the approach-avoidance task spent more time reading smoking-related information. An approach-avoidance task is a potentially feasible strategy for changing implicit attitudes toward smoking and increasing receptivity to smoking-related information

Advancing the Expectancy Concept via the Interplay Between Theory and Research

Four papers from a 2001 Research Society on Alcoholism symposium on expectancy theory and research are summarized. The symposium contributors describe recent advances in expectancy theory and discuss their implications for assessment and for understanding the processes of development and change in the behavioral domain of alcohol use. First, findings are integrated across the diverse domains in which the expectancy concept has been applied. Second, the implications of expectancy theory for the measurement of expectancy structure and process are examined. Third, research and theory regarding alcohol expectancy development and change are presented, with an emphasis on the role of expectancies as mediators of known antecedents of drinking. Finally, an experimental procedure for investigating the causal role of expectancies is described, together with its implications for theory testing and prevention or intervention programming. Collectively, the symposium contributions demonstrate the utility of an integrated expectancy theory for the generation of innovative research operations and new insights regarding behavior development and change. Consistent with the notion of consilience, expectancy theory has demonstrated a convergence of findings across different levels of analysis, as well as across different operations, methods, and research designs