Gene expression patterns and profile changes pre- and post-erlotinib treatment in patients with metastatic breast cancer.

PURPOSE: To delineate gene expression patterns and profile changes in metastatic tumor biopsies at baseline and 1 month after treatment with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib in patients with metastatic breast cancer. EXPERIMENTAL DESIGN: Patients were treated with 150 mg of oral erlotinib daily. Gene expression profiles were measured with Affymetrix U133A GeneChip and immunohistochemistry was used to validate microarray findings. RESULTS: Estrogen receptor (ER) status by immunohistochemistry is nearly coincided with the two major expression clusters determined by expression of genes using unsupervised hierarchical clustering analysis. One of 10 patients had an EGFR-positive tumor detected by both microarray and immunohistochemistry. In this tumor, tissue inhibitor of metalloproteinases-3 and collagen type 1 alpha 2, which are the EGF-down-regulated growth repressors, were significantly increased by erlotinib. Gene changes in EGFR-negative tumors are those of G-protein-linked and cell surface receptor-linked signaling. Gene ontology comparison analysis pretreatment and posttreatment in EGFR-negative tumors revealed biological process categories that have more genes differentially expressed than expected by chance. Among 495 gene ontology categories, the significant differed gene ontology groups include G-protein-coupled receptor protein signaling (34 genes, P = 0.002) and cell surface receptor-linked signal transduction (74 genes, P = 0.007). CONCLUSIONS: ER status reflects the major difference in gene expression pattern in metastatic breast cancer. Erlotinib had effects on genes of EGFR signaling pathway in the EGFR-positive tumor and on gene ontology biological process categories or genes that have function in signal transduction in EGFR-negative tumors.     

Longitudinal,population-based study of racial/ethnic differences in colorectal cancer survival: impact of neighborhood socioeconomic status,treatment and comorbidity

Background  

Colorectal cancer, if detected early, has greater than 90% 5-year survival. However, survival has been shown to vary across racial/ethnic groups in the United States, despite the availability of early detection methods.     

Changes in sleep polygraphic variables and clinical state in depressed patients during treatment with citalopram

Drug-induced improvement of depression may be mediated by changes in sleep physiology. The aim of this study was to relate changes in sleep polygraphic variables to clinical state during treatment with citalopram, a highly specific serotonin uptake inhibitor. Sixteen patients took part. The study was single-blind and uncontrolled. A 1-week wash-out period was followed by 1 week of placebo administration, a medication period of 5 weeks, and a 1-week placebo period. For the entire group a significant decrease of rapid eye movement sleep (REMS) and a significant lengthening of REMS latency were observed initially as well as at the end of treatment. No changes in sleep continuity were found, but non-REMS stage 2 (percentage) was significantly increased. On the basis of clinical change, as expressed by the scores of the Hamilton Rating Scale for Depression, at the end of the citalopram treatment the patient group was split in two halves: eight less and eight more improved patients. The groups did not differ with respect to any sleep polygraphic varible.     

Multiple familial angiolipomatosis: treatment of liposuction

Lipomas constitute the most common soft-tissue tumors [11] and may occur sporadically or as one of several inherited disorders. Benign fatty tumors can be classified into three major categories: solitary lipomas, familial multiple lipomatosis, and congenital diffuse lipomatosis [4]. The latter has also been referred to as multiple symmetric lipomatosis, Madelung's disease, or Launois-Bensaude syndrome. Within the categories a more vascular varient of the lipoma, the angiolipoma, has been described separately by some authors, but in many reports it is not distinguished from a lipoma. Liposuction has been used for the treatment of solitary lipomas, but to our knowledge liposuction has not previously been reported for excision of angiolipomas or in familial cases involving multiple lipomas as described here.     

Pravastatin therapy is associated with reduction in coronary allograft vasculopathy in pediatric heart transplantation.

BACKGROUND: Hydroxymethylglutaryl CoA reductase inhibitors (statins) have been demonstrated to reduce the risk of developing coronary allograft vasculopathy (CAV) following heart transplantation in adults and are used routinely in many centers. CAV and lipid abnormalities have been reported to be less prevalent in pediatric heart transplant recipients. It is not known whether statins reduce the risk of CAV in this population METHODS: A retrospective review was performed to analyze the risk factors for developing CAV following pediatric heart transplantation with particular attention to the impact of pravastatin therapy. The study population was comprised of 129 pediatric patients who underwent 142 heart transplants at our institution from 1988 to 2003. The outcome variable was freedom from CAV, CAV being determined by coronary angiography or autopsy. RESULTS: CAV was identified in 25 recipients at a median of 3.7 years after transplantation. There were 331 patient-years of pravastatin therapy. Pravastatin therapy resulted in a reduction in total cholesterol levels, 162 +/- 29 to 137 +/- 20 mg/dl, p = 0.01. In multivariate analysis the use of pravastatin was associated with a lower incidence of CAV (p = 0.03), whereas an increased frequency of late rejection (p = 0.003) and earlier year of transplantation (p = 0.04) were associated with increased risk of CAV. CONCLUSIONS: The routine use of pravastatin was associated with a lower risk following pediatric heart transplantation. Further studies into the relationship between lipid abnormalities, inflammation and rejection, and the development of CAV in children are warranted.     

5-HT1B Receptor Polymorphism and Clinical Response to Sumatriptan

The 5-HT₁ receptor agonist, sumatriptan, is highly effective in the treatment of migraine. Some patients, however, do not respond or experience recurrence of the headache. In addition, some patients report chest symptoms after sumatriptan. We investigated whether these different responses could be attributed to genetic diversity of the 5-HT_1B receptor, which most likely mediates the therapeutic action and the coronary side effects of sumatriptan. Allele frequencies of two polymorphisms in the 5-HT_1B receptor gene ( G861C and T-261G ) were investigated in migraine patients with consistently good response to sumatriptan (n=14), with no response (n=12), with recurrence of the headache (n=12), with chest symptoms (n=13), and in patients without chest symptoms (n=27). Allele frequencies (G:0.74; C:0.26 at nt 861 and T:0.39; G:0.61 at nt -261) did not differ between patient groups, indicating that genetic diversity of the 5-HT_1B receptor does not seem to be involved in the different clinical responses to sumatriptan.     

The reliability and validity of the Seasonal Pattern Assessment Questionnaire: a comparison between patient groups

Background: The Seasonal Pattern Assessment Questionnaire (SPAQ) is a frequently used screening instrument in the research on Seasonal Affective Disorder (SAD). Nevertheless, studies on its reliability and validity are relatively scarce. In the present study the reliability and the contrast validity of the SPAQ are investigated. Methods: SAD patients, selected by means of a clinical interview, non-seasonal depressed out-patients, non-depressed out-patients, and a control group, are contrasted to estimate the discriminating power of the SPAQ. Also, the reliability and factor structure of the seasonality and the climate subscales are investigated. To study food intake the Seasonal Food Preference Questionnaire (SFPQ) was developed. Results: The SAD criterion of the SPAQ shows good specificity (94%), but a low sensitivity (44%). Discriminant analysis shows sufficient ability to classify subjects (81% correctly classified). The Global Seasonality Scale has a good internal consistency. It consists of two factors, a psychological factor and a food factor. The SFPQ is sensitive for carbohydrate intake by SAD patients. Limitations: Most SAD patients had received treatment and completed the SPAQ while they were not depressed, which may have influenced the sensitivity. Conclusions: The SPAQ is not sensitive enough to be considered a diagnostic instrument for SAD. Nevertheless, it is accurate enough to be used as a screenings instrument. The only false positives were found in the depressive group. The accuracy of prevalence Figs. can be improved by completion of the SPAQ in the summer months, combined with the completion of a depression scale.