Significant Frequency of Allelic Imbalance in 3p Region Covering RAR? and MLH1 Loci Seems to Be Essential in Molecular Non-Small Cell Lung Cancer Diagnosis.
Significant frequency of allelic imbalance in 3p region covering RAR? and MLH1 loci seems to be essential in molecular non-small cell lung cancer diagnosis.
Med Oncol. 2013 Jun; 30(2): 532
Antczak A, Migdalska-S?k M, Pastuszak-Lewandoska D, Czarnecka K, Nawrot E, Doma?ska D, Kordiak J, Górski P, Brzezia?ska E
The aim of the study was to investigate the influence of allelic imbalance (AI) in several loci of tumor suppressor genes in 3p region on the non-small cell lung cancer (NSCLC) development. We evaluated the frequency of loss of heterozygosity and/or microsatellite imbalance (LOH/MSI) and assessed their association with patients’ characteristics (age, gender, tobacco addiction) and NSCLC classification according to TNM/AJCC staging. To analyze the potential role of AI involved in NSCLC pathogenesis, we allelotyped a group of 74 NSCLC patients using 7 microsatellite markers. The highest frequency of LOH/MSI, however, not statistically significant, was observed in RAR? and MLH1 (p = 0.104 and p = 0.216, respectively) loci. The association between high LOH/MSI frequency in 3p region with male gender (p = 0.041) as well as with age (especially >60 years) for RAR? and MLH1 genes (p = 0.0001 and p = 0.020, respectively) was documented. Statistically significant increased frequency of MLH1 allelic loss in squamous cell carcinoma (SCC) versus non-squamous cell carcinoma (non-SCC) was observed (p = 0.01). Significant increase in LOH/MSI frequency in 3p region (mainly in FHIT and MLH1 loci) in correlation with cigarette addiction in a lifetime (?40 years and ?40 Pack Years) was also documented (p < 0.05). The highest LOH/MSI was revealed in RAR? locus in IA tumors (p = 0.0001), while the similarly high allelic loss of MLH1 correlated with III A/B tumors (p = 0.0002), according to AJCC staging. The obtained results demonstrate that AI is influenced by tobacco smoking and seems to be vital in the molecular diagnosis of NSCLC, especially of SCC subtype. HubMed – addiction
Mechanisms and insights into drug resistance in cancer.
Front Pharmacol. 2013; 4: 28
Zahreddine H, Borden KL
Cancer drug resistance continues to be a major impediment in medical oncology. Clinically, resistance can arise prior to or as a result of cancer therapy. In this review, we discuss different mechanisms adapted by cancerous cells to resist treatment, including alteration in drug transport and metabolism, mutation and amplification of drug targets, as well as genetic rewiring which can lead to impaired apoptosis. Tumor heterogeneity may also contribute to resistance, where small subpopulations of cells may acquire or stochastically already possess some of the features enabling them to emerge under selective drug pressure. Making the problem even more challenging, some of these resistance pathways lead to multidrug resistance, generating an even more difficult clinical problem to overcome. We provide examples of these mechanisms and some insights into how understanding these processes can influence the next generation of cancer therapies. HubMed – addiction
Effects of the beta-lactam antibiotic ceftriaxone on nicotine withdrawal and nicotine-induced reinstatement of preference in mice.
Psychopharmacology (Berl). 2013 Mar 16;
Alajaji M, Bowers MS, Knackstedt L, Damaj MI
RATIONALE: Several studies suggest that repeated nicotine administration causes alterations in glutaminergic transmission that may play an important role in developing and maintaining nicotine addiction. Chronic nicotine administration in rats decreases the expression of the glutamate transporter-1 (GLT-1) and cysteine-glutamate exchanger (system xC-) in the nucleus accumbens. We hypothesized that ceftriaxone, a GLT-1 and system xC- activator, would decrease murine behavioral aspects of nicotine dependence. OBJECTIVE: This study aimed to investigate the effect of repeated ceftriaxone administration on the behavioral effects of nicotine using mouse models of conditioned reward and withdrawal. METHOD: Using male ICR mice, the ability of repeated ceftriaxone injections to modulate the development and reinstatement of a nicotine-conditioned place preference (CPP) was evaluated. Additionally, nicotine withdrawal-associated signs were assessed. These included both physical (somatic signs and hyperalgesia) and affective (anxiety-related behaviors) withdrawal signs in mice. Finally, the effects of ceftriaxone on nicotine-induced antinociception and hypothermia after acute nicotine injection were measured. RESULT: Ceftriaxone had no effect on the development of nicotine preference but significantly attenuated nicotine-induced reinstatement of CPP. Furthermore, ceftriaxone reversed all nicotine withdrawal signs measured in mice. CONCLUSION: Altogether, these findings show that a ?-lactam antibiotic reduces nicotine withdrawal and nicotine-seeking behavior. Our results suggest that the documented efficacy of ceftriaxone against cocaine and morphine dependence-related behaviors effects extends to nicotine. HubMed – addiction
Addiction Postulates and Legal Causation, or Who’s in Charge, Person or Brain?
J Am Acad Psychiatry Law. 2013; 41(1): 92-7
Wallace DL
In this article, I address the persistent confusion over the meaning of a medical diagnosis of drug addiction or substance dependence in the courtroom, specifically in regard to legal judgments about the reasonable legal person, causation, and individual responsibility in civil actions. Using the example of the Engle tobacco litigation in Florida, where the plaintiffs have reduced mind to brain and claimed that the clinical status of addiction excuses or mitigates the smoker’s responsibility for the health consequences of smoking based on brain processes, I examine the conceptual difficulties presented by use of biomedical models of behavior in a legal system predicated on different assumptions altogether. For legal purposes, the biological system in question is the human organism as a whole, not a brain per se, and there is a functional identity between a smoker and his motivational states for purposes of responsibility attribution. HubMed – addiction
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