No abstract

Many chronic medical disorders are associated with psychiatric morbidity. Yet the psychological burden of these disorders often goes unnoticed. In dermatology, psoriasis has a higher association with psychiatric illness, including depression and suicide risk, compared with many other conditions. Studies suggest that effective treatment of psoriasis results in the improvement of psychiatric morbidity, particularly depression and anxiety. New biologic treatments for psoriasis may offer help beyond clearing of the skin in these patients and may lead to a reduction of psychiatric morbidity. Although concerns have been raised regarding the potential link between interleukin-17R blockade in the treatment of psoriasis and suicide, current literature provides no evidence to support this association.

PurposeTo provide consensus recommendations on the use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with advanced or metastatic non-small-cell lung cancer (NSCLC). MethodsUsing a systematic literature search, phase II trials, randomized phase III trials, and meta-analyses were identified for inclusion. ResultsA total of forty-six trials were included. Clear evidence is available that EGFR-TKIs should not be administered concurrently with platinum-based chemotherapy as first-line therapy in advanced or metastatic NSCLC. Evidence is currently insufficient to recommend single-agent EGFR-TKIs as first-line therapy either in unselected populations or in populations selected on the basis of molecular or clinical characteristics. Following failure of platinum-based chemotherapy, the evidence suggests that second-line EGFR-TKIs or second-line chemotherapy result in similar survival. Quality of life and symptom improvement for patients treated with an EGFR-TKI appear better than they do for patients treated with second-line docetaxel. Sequence of therapy may not appear to be important, but if survival is the outcome of interest, the goal should be to optimize the number of patients receiving three lines of therapy. Based on available data, molecular markers and clinical characteristics do not appear to be predictive of a differential survival benefit from an EGFR-TKI and therefore those factors should not be used to select patients for EGFR-TKI therapy. ConclusionsThe EGFR-TKIs represent an additional therapy in the treatment of advanced or metastatic NSCLC. The results of ongoing clinical trials may define the optimal role for these agents and the effectiveness of combinations of these agents with other targeted agents. KEY WORDSNon-small-cell lung cancer, targeted therapy, epidermal growth factor receptor, tyrosine kinase inhibitor, molecular marker

Fanconi anemia (FA) is a genetically heterogeneous, autosomal recessive disorder characterized by a variety of congenital and skeletal malformations, progressive pancytopaenia and predisposition to malignancies. While the basic defect in this disease is not known, the cloning of the gene defective in FA group C patients (FAC) allows analysis of its expression pattern, which may provide clues about the functional properties of the protein. This paper describes the distribution of Fac transcripts during murine development (8-19.5 days p.c.), using RNA in situ hybridization. Fac is initially expressed (8-10 days p.c.) in the mesenchyme and its derivatives with osteogenic potential. The transcript is also apparent at later stages of bone development (13-19.5 days p.c.), localized to cells of the inner perichondrium, periosteum and zone of endochondral ossification. In the latter, Fac transcripts are seen in cells from both osteogenic and hematopoietic lineages. Fac mRNA is also seen in intramembranous cranial and facial bones. In addition, Fac signal is detected in non-skeletal tissues: brain, whisker follicles, lung, kidney, gut and stomach. Fac expression is high in progenitor cell populations but is downregulated in differentiating cells that give rise to connective tissue. The pattern of Fac expression is consistent with the skeletal and non-skeletal congenital abnormalities in FA patients. As well, expression in rapidly dividing progenitors is consistent with hypotheses regarding the nature of the basic defect in FA: a role of the protein in DNA repair or protection from oxygen toxicity.