Tobacco, alcohol, cannabis and other illegal drug use among young adults: the socioeconomic context

Background

Low socioeconomic position predicts risk of substance abuse, yet few studies tested the role of preexisting familial and individual characteristics.

Methods

Data come from the TEMPO (Trajectoires Epidémiologiques en Population) study (community sample in France, 1991–2009, n = 1103, 22–35 years in 2009) set up among offspring of participants of an epidemiological study (GAZEL). Past 12-month substance use was assessed in 2009 by self-completed mail survey: regular tobacco smoking, alcohol abuse (AUDIT), cannabis use, problematic cannabis use (CAST), other illegal drug use. Socioeconomic position was defined by educational attainment, occupational grade, employment stability and unemployment. Covariates included demographics (age, sex, relationship status, parenthood), family background (parental income, parental tobacco smoking, parental alcohol use), and juvenile characteristics (psychological problems, academic difficulties) measured longitudinally.

Results

35.8% of study participants were regular smokers, 14.3% abused alcohol, 22.6% used cannabis (6.3% had problematic cannabis use) and 4.1% used other illegal drugs. Except for alcohol abuse, substance use rates were systematically higher in individuals with low, rather than intermediate/high, socioeconomic position (age and sex-adjusted ORs from 1.75 for cannabis use to 2.11 for tobacco smoking and 2.44 for problematic cannabis use). In multivariate analyses these socioeconomic disparities were decreased, but remained statistically significant (except for illegal drugs other than cannabis).

Conclusions

Tobacco smoking, alcohol, cannabis and polysubstance use are common behaviors among young adults, particularly those experiencing socioeconomic disadvantage. Interventions aiming to decrease substance abuse and reduce socioeconomic inequalities in this area should be implemented early in life.     

A simple method for the routine detection of somatic quantitative genetic alterations in colorectal cancer

BACKGROUND & AIMS: Several quantitative genetic alterations have been suggested to have in colorectal cancer (CRC) either a prognostic or a therapeutic predictive value. Routine detection of these alterations is limited by the absence of simple methods. METHODS: The somatic quantitative multiplex polymerase chain reaction of short fluorescent fragments (QMPSF) is based on the simultaneous amplification under quantitative conditions of several dye-labeled targets both from tumor and nonmalignant tissues. For each patient, the resulting QMPSF fluorescent profiles are superimposed, and quantitative changes are simply detected by an increase or decrease of the corresponding fluorescent peaks. Two assays were developed and applied to 57 CRC: a "bar code" exploring several loci with known prognostic value and a "kinogram" studying the copy number change of kinase genes, against which inhibitors have been developed. RESULTS: The bar code revealed that the most frequent alterations were the gain of AURKA/20q13 (53%) and MYC/8q24 (39%) and heterozygous deletion of DCC/18q21.3 (39%) and TP53/17p13 (23%). The kinogram detected a gene copy number increase for AURKA, PTK2, MET, and EGFR in 53%, 37%, 33%, and 28% of the tumors, respectively. QMPSF results were validated by comparative genomic hybridization and multiplex real-time polymerase chain reaction on genomic DNA. CONCLUSIONS: The somatic QMPSF is a simple method able to detect simultaneously on a routine basis several quantitative changes in tumors. Its flexibility will allow the integration of clinically relevant genes. This high throughput method should be a valuable complementary tool of fluorescent in situ hybridization and comparative genomic hybridization.     

Examination of concordance between maternal and youth reports in the diagnosis of pediatric bipolar disorder

Objective:  While concordance between mother and child report continues to be the gold standard in the assessment of pediatric bipolar disorder, uncertainty develops when a mother's report is not endorsed by the youth. To this end we compared discordant (mother positive and youth negative) and concordant (mother and youth positive) cases.
Methods:  Subjects were 98 adolescents (12–19 years of age) derived from family studies of bipolar disorder in youth who had both self-reported and mother-reported assessments. Comparisons were made between discordant (n = 35) and concordant (n = 59) cases on a wide range of clinical correlates.
Results:  Mothers in both groups reported similar rates of symptoms of mania and depression. Within the concordant group, mothers and youth reported similar rates of symptoms of mania. There were no differences between the concordant and discordant groups in onset, duration, or impairment of mania, rates of psychiatric hospitalization, cognitive variables, or rates of disorders in family members.
Conclusions:  The similarities between discordant and concordant reports in symptomatology of mania and depression, rates of comorbidities, treatment needs, and other clinical correlates suggest that a mother-based diagnosis of mania should not be discounted in discrepant cases in which the youth fails to endorse the diagnosis.     

Animal models of chemotherapy-evoked painful peripheral neuropathies

This review examines recent preclinical research on toxic peripheral neuropathy and potential therapeutic developments. Chemotherapy-induced peripheral neurotoxicity is a major clinical problem because it represents the dose-limiting side effects of a significant number of antineoplastic drugs. Patients are unable to complete full or optimal treatment schedules. The incidence of chemotherapy-induced peripheral neuropathy varies depending on the drugs and schedules used, and this can be quite high, particularly when neurophysiological methods are used to make a diagnosis. However, even when chemotherapy-induced peripheral neuropathy is not a dose-limiting side effect, its onset may severely affect the quality of life of cancer patients and cause chronic discomfort. As such, improved understanding of the pathophysiology of chemotherapy-induced neurotoxicity need for animal models is clinically relevant and will assist in the development of future neuroprotective strategies and also in the design of novel chemotherapies with improved toxicity profiles. In this review, the features of animal models of chemotherapy-induced painful neuropathy developed for 20 years, due to the administration of the most widely used drugs, such as platinum drugs, taxanes, and vinca alkaloids, will be discussed. In a second part, data available on neuroprotectants and treatment strategies, evaluated using these previous animal models in the attempt to prevent neuropathic pain, will be summarized.     

Nck2 promotes human melanoma cell proliferation, migration and invasion in vitro and primary melanoma-derived tumor growth in vivo

Background

Nck1 and Nck2 adaptor proteins are involved in signaling pathways mediating proliferation, cytoskeleton organization and integrated stress response. Overexpression of Nck1 in fibroblasts has been shown to be oncogenic. Through the years this concept has been challenged and the consensus is now that overexpression of either Nck cooperates with strong oncogenes to transform cells. Therefore, variations in Nck expression levels in transformed cells could endorse cancer progression.

Methods

Expression of Nck1 and Nck2 proteins in various cancer cell lines at different stages of progression were analyzed by western blots. We created human primary melanoma cell lines overexpressing GFP-Nck2 and investigated their ability to proliferate along with metastatic characteristics such as migration and invasion. By western blot analysis, we compared levels of proteins phosphorylated on tyrosine as well as cadherins and integrins in human melanoma cells overexpressing or not Nck2. Finally, in mice we assessed tumor growth rate of human melanoma cells expressing increasing levels of Nck2.

Results

We found that expression of Nck2 is consistently increased in various metastatic cancer cell lines compared with primary counterparts. Particularly, we observed significant higher levels of Nck2 protein and mRNA, as opposed to no change in Nck1, in human metastatic melanoma cell lines compared with non-metastatic melanoma and normal melanocytes. We demonstrated the involvement of Nck2 in proliferation, migration and invasion in human melanoma cells. Moreover, we discovered that Nck2 overexpression in human primary melanoma cells correlates with higher levels of proteins phosphorylated on tyrosine residues, assembly of Nck2-dependent pY-proteins-containing molecular complexes and downregulation of cadherins and integrins. Importantly, we uncovered that injection of Nck2-overexpressing human primary melanoma cells into mice increases melanoma-derived tumor growth rate.

Conclusions

Collectively, our data indicate that Nck2 effectively influences human melanoma phenotype progression. At the molecular level, we propose that Nck2 in human primary melanoma promotes the formation of molecular complexes regulating proliferation and actin cytoskeleton dynamics by modulating kinases or phosphatases activities that results in increased levels of proteins phosphorylated on tyrosine residues. This study provides new insights regarding cancer progression that could impact on the therapeutic strategies targeting cancer.