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.     

Pregnancy and Renal Transplantation: A Case Report of the Risk of Antibody Induction Against Partner Antigens

Renal transplantation has provided women of childbearing age with increased fertility and the possibility of successful pregnancy outcomes. Approximately 14,000 births among women with transplanted organs have been reported worldwide, but pregnancy complications have been frequent: spontaneous or therapeutic abortion, preterm birth, low birth weight, and intrauterine growth restriction. Herein we have described a case of an acute rejection episode in a renal transplant recipient, occurring 6 months after successful delivery, despite the fulfillment of all European best practice guidelines criteria and the maintenance of adequate immunosuppression. Our case demonstrated that even a presumably low-risk patient can face worsening of renal function during or after pregnancy. Acute immune activation is uncommon but may occur in late-onset fashion. Despite adequate levels of maintenance immunosuppression, there is a risk of developing antibodies against the partner or the donor, causing acute renal immune damage.     

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.     

Cartilage destruction in small joints by rheumatoid arthritis: assessment of fat-suppressed three-dimensional gradient-echo MR pulse sequences in vitro

Purpose. To assess the accuracy of different MR sequences for the detection of articular cartilage abnormalities in rheumatoid arthritis. Design and patients. Ten metacarpophalangeal joints and 10 metatarsophalangeal joints (specimens from arthritis patients undergoing ablative joint surgery) were examined with a fat-suppressed (FS) 3D FLASH, a FS 3D FISP, a FS 2D fast spin-echo T2-weighted, and a 2D FS spin-echo T1-weighted sequence. Each cartilage lesion and each cortical lesion was graded from 0 to 4 (modified Outerbridge staging system). Subsequently, the results of each sequence were compared with the macroscopic findings and statistically tested against each other. Results. The study shows that 3D gradient-echo sequences with fat suppression were best for imaging and grading of cartilage lesions in arthritis of the small joints of the hands and feet. Using 3D techniques, all grade 2, grade 3, and grade 4 lesions of cartilage or cortical bone were detected. Conclusion. FS 3D gradient-echo techniques were best for the detection and grading of hyaline cartilage and subchondral bone lesions in rheumatoid arthritis. MRI has a great potential as an objective method of evaluating cartilage damage and bone erosions in rheumatoid arthritis.     

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.     

Expression of Matrix Metalloproteinases and Their Tissue Inhibitors in Human Brain Tumors

In this study, we investigated the expression patterns of 15 matrix metalloproteinases (MMPs) and three tissue inhibitors of metalloproteinase in gliomas, medulloblastomas, and normal brain tissue. By Northern blot analysis we found increased levels of mRNAs encoding for gelatinase A, gelatinase B, two membrane-type MMPs (mt1- and mt2-MMP), and tissue inhibitors of metalloproteinase-1 in glioblastomas and medulloblastomas. We observed a significant increase of mt1-MMP, gelatinase A, gelatinase B, and tissue inhibitors of metalloproteinase-1 in glioblastomas as compared with low-grade astrocytomas, anaplastic astrocytomas, and normal brain. In medulloblastomas, the expression of mt1-MMP, mt2-MMP, and gelatinase A were also increased, but to a lesser extent than that observed in glioblastomas. These data were confirmed at the protein level by immunostaining analysis. Moreover, substrate gel electrophoresis showed that the activated forms of gelatinases A and B were present in glioblastomas and medulloblastomas. These results suggest that increased expression of mt1-MMP/gelatinase A is closely related to the malignant progression observed in gliomas. Furthermore, the present study demonstrates, to our knowledge for the first time, that medulloblastomas express high levels of MMP.