Biomedical subjects

Ran Wu

Publications and source records attributed to Ran Wu.

11 recordsLinked to original sources

PubMed2007

New insights into the efficacy of naltrexone based on trajectory-based reanalyses of two negative clinical trials.

BACKGROUND: The heterogeneity of clinical findings in studies evaluating the efficacy of naltrexone in the treatment of alcohol dependence has led to growing efforts to explore novel approaches to data analysis. The objective of this study was to identify distinct trajectories of daily drinking over time in two negative clinical trials and to determine whether naltrexone affected the probability to follow a particular trajectory. METHODS: The Veterans Affairs (VA) Cooperative Study #425 and the Women's Naltrexone Study failed to demonstrate efficacy on primary outcome variables. Separately for each study, we analyzed daily indicators of any drinking and heavy drinking using a semiparametric group-based approach. RESULTS: We estimated three distinct trajectories of daily drinking (both any and heavy drinking) which we described as "abstainer," "sporadic drinker," and "consistent drinker." Naltrexone doubled the odds of following the abstainer trajectory instead of the consistent drinker trajectory but did not significantly change the odds of following the abstainer trajectory as contrasted with the sporadic drinker trajectory. CONCLUSIONS: Naltrexone may have a clinically meaningful effect for alcohol-dependent patients with a high chance of consistent drinking, even in studies where it failed to show efficacy in planned analyses.

Adult↗

PubMed2006

Cigarette smoke condensate and dioxin suppress culture shock induced senescence in normal human oral keratinocytes.

The aryl hydrocarbon receptor is a ligand activated transcription factor which regulates biological responses to a variety of environmental pollutants, such as dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) and cigarette smoke. The purpose of this study was to determine whether cigarette smoke condensate (CSC) is capable of activating the AHR in normal human oral keratinocytes (NHOK) and inhibiting their ability to senesce. Towards this end, NHOK were isolated from human subjects and were cultured in the presence or absence of either TCDD or CSC. While neither TCDD nor CSC treatments altered the lifespan of NHOK in culture, both were capable of suppressing a culture induced premature senescence as indicated by their ability to decrease the mRNA and protein levels of the senescence markers p16(INK4a), p53 and p15(INK4b). A role of the AHR in mediating these events is indicated by the observations that the TCDD and CSC-induced decreases in p15(INK4b), p16(INK4a) and p53 expression was accompanied by a corresponding increase in the expression levels of the AHR target gene, CYP1A1. In addition, cotreatment with the AHR antagonist, 3'-methoxy-4'-nitroflavone (MNF) blocked the effects of TCDD and CSC on p53 and CYP1A1 expression. The findings of this study indicate that in NHOK, CSC is capable of altering a key cell fate decision, i.e., commitment to premature senescence, that is in part, dependent on the AHR. These results support the idea that progression of CSC-induced tumorigenesis may include an AHR-mediated inhibition of senescence that contributes to immortalization and agents that block the actions of the AHR may be effective components of novel cancer therapeutics.

Blotting, Western↗

PubMed2006

Lack of the aryl hydrocarbon receptor leads to impaired activation of AKT/protein kinase B and enhanced sensitivity to apoptosis induced via the intrinsic pathway.

The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor that is best known for its role in mediating the toxicity of many environmental contaminants such as 2,3,7,8 tetrachlorodibenzo-p-dioxin. However, the endogenous role of AHR, especially with respect to the apoptotic process, is largely unknown and contradictory. In this report, we have used a mouse hepatoma cell line (Hepa1c1c7) and its AHR-deficient derivative (LA1) to examine the effect of differing AHR levels on apoptosis susceptibility, in particular, apoptosis regulated by the intrinsic pathway. Toward this end, the cells were subjected to UV irradiation, hydrogen peroxide, and serum starvation. Analyses of a number of different endpoints of apoptosis revealed that the LA1 cells were more sensitive to these stresses than the wild-type cells, indicating that the AHR plays a cytoprotective role in the face of stimuli that initiate the intrinsic apoptotic pathway. A direct role of the AHR in mediating this effect was confirmed using both pharmacological and molecular approaches. Further analyses imply that lack of the AHR leads to an impaired survival response mediated by phosphatidylinositol 3'-OH kinase-Akt/protein kinase B and, to a lesser degree, epidermal growth factor receptor activation. These findings indicate that exploring the use of the AHR antagonist as agents that enhance the proapoptotic actions of cancer therapies may be a valid approach.

Animals↗

PubMed2006

Characteristics of older adult problem gamblers calling a gambling helpline.

BACKGROUND: Few investigations have characterized groups of older adults with gambling problems, and published reports are currently limited by small samples of older adult problem gamblers. Gambling helplines represent a widespread mechanism for assisting problem gamblers to move into treatment settings. Given data from older adult problem gamblers in treatment, we hypothesized that older as compared with younger adult problem gamblers calling a gambling helpline would be less likely to report gambling-related problems. DESIGN AND METHODS: Logistic regression analyses were performed on data obtained from January 1, 2000 to December 31, 2001, inclusive, from callers with gambling problems (N = 1,084) contacting the Connecticut Council on Problem Gambling Helpline. RESULTS: Of the 1,018 phone calls used in the logistic regression analyses, 168 (16.5%) were from older adults and 850 (83.5%) from younger adults. Age-related differences were observed in demographic features, types and patterns of gambling reported as problematic, gambling-related problems and psychiatric symptoms, substance use problems, patterns of indebtedness, and family histories of addictive disorders. Older as compared with younger adult problem gamblers were more likely to report having lower incomes, longer durations of gambling, fewer types of problematic gambling, and problems with casino slot machine gambling and less likely to report gambling-related anxiety, family problems, illegal behaviors and arrests, drug problems, indebtedness to bookies or acquaintances, family histories of drug abuse, and problems with casino table gambling. CONCLUSIONS: Older as compared with younger adult problem gamblers calling a gambling helpline differ on many clinically relevant features. The findings suggest the need for improved and unique prevention and treatment strategies for older adults with gambling problems.

Adult↗

PubMed2006

A decrease in the plasma DHEA to cortisol ratio during smoking abstinence may predict relapse: a preliminary study.

RATIONALE: Increases in depressive symptoms during smoking cessation have been associated with risk for relapse. Several studies have linked plasma levels of cortisol and dehydroepiandrosterone (DHEA) or DHEA-sulfate (DHEAS) to depressive symptoms. OBJECTIVES: To determine whether changes in plasma cortisol, DHEA, or DHEAS levels and emergence of depressive symptoms during smoking cessation are associated with smoking relapse. MATERIALS AND METHODS: Subjects were healthy non-medicated men and women, aged 39+/-12 years, who smoked, on average, 22 cigarettes per day. Depressive symptoms, smoking withdrawal symptoms, and plasma steroid levels were measured before and after 8 days of verified smoking abstinence. Relapse status at day 15 was then determined. RESULTS: In the full sample (n=63), there was a trend for changes in depressive symptoms to be associated with relapse. In the subset of 25 subjects with plasma neuroactive steroid data, there was a significant interaction between the change in the plasma DHEA/cortisol ratio from day 0 to day 8 and relapse status at day 15. This ratio was similar before abstinence, but lower at day 8 in relapsed, compared to abstinent, subjects. Changes in the DHEA/cortisol ratio tended to predict changes in depressive symptoms in the women only. CONCLUSION: A decrease in the plasma DHEA/cortisol ratio during 8 days of smoking abstinence was associated with relapse over the following week. Further research is needed to fully characterize sex-specific relationships between abstinence-induced changes in neuroactive steroid levels, depressive or withdrawal symptoms, and relapse. Such research may lead to new interventions for refractory smoking dependence.

Adult↗

PubMed2006

A controlled trial of naltrexone augmentation of nicotine replacement therapy for smoking cessation.

BACKGROUND: Many smokers remain refractory to current therapies, which only partially address weight gain after smoking cessation. Thus, this study evaluated whether naltrexone hydrochloride augmentation of nicotine patch therapy improves smoking abstinence and reduces postcessation weight gain more than nicotine patch therapy alone and at what dose. METHODS: Six-week double-blind placebo-controlled trial with follow-up in an outpatient research center. Four hundred individuals who smoked 20 or more cigarettes daily were randomly assigned to treatment for 6 weeks with a 21-mg nicotine patch and oral naltrexone hydrochloride (0, 25, 50, or 100 mg/d) after equal random treatment assignment and followed up for 1 year after randomization. The a priori specified primary end points were prolonged 4-week cigarette abstinence after a 2-week grace period in the intent-to-treat sample and weight gain in these abstainers. RESULTS: We found no significant differences in prolonged 4-week abstinence (P = .49) or 6-week continuous abstinence after the quit date (P = .12) during treatment in the intent-to-treat analysis. Among 295 treatment completers, the 100-mg dose was associated with higher continuous abstinence rates (71.6%) compared with placebo (48%) (odds ratio, 2.73; 95% confidence interval, 1.39-5.39; P<.01). Among continuous abstainers, the 25-mg naltrexone hydrochloride group gained significantly less weight (mean +/- SEM, 0.7 +/- 0.31 kg) than the placebo group (mean +/- SEM, 1.9 +/- 0.33 kg; P<.01). Similar naltrexone dose effects on weight were found for those with prolonged abstinence and treatment completers, irrespective of abstinence. CONCLUSIONS: The 100-mg dose of naltrexone hydrochloride appears the most promising for augmenting the efficacy of the nicotine patch on smoking cessation outcomes but requires further study. The significant weight reduction with low-dose naltrexone therapy suggests that it may be useful as a second-line treatment for weight-concerned smokers.

Administration, Cutaneous↗

PubMed2005

Characteristics of gambling helpline callers with self-reported gambling and alcohol use problems.

The characteristics of problem gamblers calling the Connecticut Council on Problem Gambling (CCPG) gambling helpline during the years 2000-2001 (n = 960) were examined based on the presence or absence of self-reported alcohol use problems. A relatively low proportion of callers reported a problem with alcohol use (173/960 or 18.0%), and of those acknowledging an alcohol use problem, the majority reported a past rather than current problem (143/173 or 82.7%). A logistic regression analysis found that, as compared with problem gamblers denying any alcohol use problems, those reporting past or current alcohol use problems were more likely to be male and more frequently acknowledged problems with more forms of gambling, suicide attempts related to gambling, arrests secondary to gambling, daily tobacco use, drug use problems, prior substance abuse treatment, and family histories positive for alcohol and drug use problems. The findings highlight the strong relationship between alcohol use problems and other substance use problems, and suggest that problem gamblers with as compared with those without alcohol use problems demonstrate greater problems in multiple areas (arrest, attempted suicide) linked by impaired impulse control.

Adult↗

PubMed2005

Self-reported gambling-related suicidality among gambling helpline callers.

Problem gamblers often attribute suicidal ideation or attempts to their gambling. Logistic regression analyses were applied to data from problem gamblers (N = 986) calling a helpline. Problem gamblers reporting gambling-related suicidality (n = 252; 25.6%) were more likely than those denying it (n = 734; 74.4%) to acknowledge family, financial, legal, and mental and substance-related problems. Of problem gamblers acknowledging gambling-related suicidality, those reporting gambling-related suicide attempts (n = 53; 21.5%) were more likely than those denying them (n = 193; 78.5%) to acknowledge gambling-related illegal behaviors, mental health and substance abuse treatment, and family histories of alcohol problems, and were less likely to report prior gambling treatment. The findings suggest that increased gambling severity is associated with gambling-related suicidality.

Adult↗

PubMed2003

ras mutations are associated with aggressive tumor phenotypes and poor prognosis in thyroid cancer.

PURPOSE: ras oncogenic activation has long been demonstrated in thyroid carcinomas of follicular cell derivation, but no consistent relationship has been shown between mutations and clinicopathologic features. MATERIALS AND METHODS: We analyzed H-, K-, and N-ras mutations by polymerase chain reaction-single-strand conformational polymorphism followed by DNA sequencing in 125 thyroid carcinoma specimens from 107 patients, to include tumors covering the entire spectrum of thyroid tumor differentiation. RESULTS: Mutations were identified in four (8.2%) of 49 well-differentiated carcinomas (WDCs; two [6.7%] of 30 of the tumors were papillary carcinomas, two [10.5%] of 19 of them were follicular carcinomas), in 16 (55.2%) of 29 poorly differentiated carcinomas (PDCs), and in 15 (51.7%) of 29 undifferentiated carcinomas, with a significant association between ras mutation and poorly or undifferentiated tumors (P <.001). Twenty-six (74.3%) of 35 patients with ras-mutated tumors died as a result of disease as opposed to 23 (31.9%) of 72 patients with tumors lacking the mutations. Among patients with differentiated thyroid carcinomas (WDC and PDC), 11 (55.0%) of 20 patients with mutated tumors died as a result of disease as opposed to nine (15.5%) of 58 patients with wild-type ras tumors, and the correlation was independent of tumor differentiation and stage (P =.016). K-ras codon 13 mutations (all with G-A nucleotide transitions resulting in Gly>Asp substitution) and single activating mutations in any of the ras genes were also independent predictors of poor survival in differentiated thyroid carcinomas (P =.027 and P =.007, respectively). CONCLUSION: These findings demonstrate that ras mutations are a marker for aggressive cancer behavior and indicate a possible role of ras genotyping to identify thyroid carcinoma subsets associated with poor prognosis.

Carcinoma, Papillary, Follicular↗

PubMed2003

Initial and maintenance naltrexone treatment for alcohol dependence using primary care vs specialty care: a nested sequence of 3 randomized trials.

BACKGROUND: Naltrexone may improve success in primary care treatment of alcohol dependence (AD). This study tests naltrexone and primary care management (PCM) vs naltrexone and cognitive behavior therapy (CBT) and tests naltrexone maintenance among patients who respond to an initial course of naltrexone combined with PCM vs CBT. METHODS: A nested sequence of 3 randomized trials was conducted. In study 1, 197 subjects with AD participated in a 10-week comparison of PCM and naltrexone (50 mg/d) vs CBT and naltrexone (50 mg/d). In study 2, 53 PCM responders from study 1 continued in a 24-week placebo-controlled study of maintenance naltrexone. In study 3, 60 CBT responders from study 1 continued in a 24-week placebo-controlled study of maintenance naltrexone and CBT. RESULTS: Study 1: No difference in the response to treatment; 84.1% (74/88) of the PCM patients and 86.5% (77/89) of the CBT patients avoided persistent heavy drinking. Percentage of days abstinent (PDA) declined over time for PCM vs CBT (P =.03). Study 2: Higher response maintenance for PCM and naltrexone (21/26, 80.8%) vs PCM and placebo (14/27, 51.9%; P =.03) and PDA declined more for the placebo group (P =.02). Study 3: The differences between naltrexone vs placebo on maintenance of response (25/30, 83.3% vs 21/30, 70.0%) or PDA did not reach statistical significance. CONCLUSIONS: Naltrexone yielded comparable results during the initial 10 weeks of treatment when combined with PCM or CBT. Maintenance of improvement was enhanced by continued naltrexone treatment in the PCM but not in the CBT arm.

Adolescent↗

PubMedDate not supplied

Characteristics of tobacco-smoking problem gamblers calling a gambling helpline.

Few studies have examined the smoking behaviors of problem gamblers. A high proportion of problem gamblers calling a gambling helpline reported daily tobacco smoking (43.1%). Problem gamblers reporting daily tobacco smoking more frequently acknowledged depression and suicidality secondary to gambling, gambling-related arrests, alcohol and drug use problems, mental health treatment, and problems with casino slot machine gambling. The findings substantiate the relationship in problem gamblers between tobacco smoking and psychiatric symptomatology, particularly other substance use problems. The high proportion of callers reporting daily tobacco smoking highlights the need for enhanced smoking cessation efforts in problem gamblers.

Adult↗