A detailed understanding of the assortment of genes that are expressed in breast tumor vessels is needed to facilitate the development of novel, molecularly targeted anti-angiogenic agents for breast cancer therapies. Rapid immunohistochemistry using factor VIII-related antibodies was performed on sections of frozen human luminal-A breast tumors (n ؍ 5) and normal breast (n ؍ 5), followed by laser capture microdissection of vascular cells. RNA was extracted and amplified, and fluorescently labeled cDNA was synthesized and hybridized to 44,000-element longoligonucleotide DNA microarrays. Statistical analysis of microarray was used to compare differences in gene expression between tumor and normal vascular cells, and Expression Analysis Systematic Explorer was used to determine enrichment of gene ontology categories. Protein expression of select genes was confirmed using immunohistochemistry. Of the 1176 genes that were differentially expressed between tumor and normal vascular cells, 55 had a greater than fourfold increase in expression level. The extracellular matrix gene ontology category was increased while the ribosome gene ontology category was decreased. Fibroblast activation protein, secreted frizzledrelated protein 2, Janus kinase 3, and neutral sphingomyelinase 2 proteins localized to breast tumor endothelium as assessed by immunohistochemistry, showing significantly greater staining compared with normal tissue. These tumor endothelial marker proteins also exhibited increased expression in breast tumor vessels compared with that in normal tissues. Therefore, these genetic markers may serve as potential targets for the development of angiogenesis inhibitors.
Porous scaffolds made from a biodegradable copolymer of trimethylene carbonate and glycolide were evaluated for tissue-engineered medical products. We examined the scaffold coated with cell adhesion protein and fibronectin and cultured under a dynamic mixing condition to enhance the growth of chondrocytes. Our hypothesis was that the combination of coating and dynamic mixing would be beneficial to the viability of the chondrocytic cells. Fibronectin was selected as the model protein because of its availability and routine assaying methods. Sterile samples of scaffolds of about 1 mm in thickness were coated with fibronectin at 37 degrees C for 1.5 h. Four groups of scaffolds were used: uncoated static or dynamic, and coated static or dynamic. Scaffold samples were placed in either a Petri dish or a spinner flask (static vs. dynamic groups) after inoculation with rat chondrocytes of an initial cell density of 1.29 x 10(5) cell/mL. After 7, 14, 21, and 28 days, each sample was fixed, embedded, and sectioned at 5 micro thickness. The sections were double-label immunostained using antibodies against cellular fibronectin synthesized by adherent cells as a measure of cell viability. A Hoechst 33258 nuclear stain was used to measure the number of cells attached to the scaffold at each time interval. The slides were examined using a fluorescence microscope to determine the cell ingrowth. At least 25 fields/treatment group (except the 7 day group) were measured. The data showed that cell in-growths into the porous scaffolds were higher at all time periods for the coated dynamic group than those for the other three groups.
2-Methoxyestradiol (2ME2), an estradiol metabolite with antiproliferative and antiangiogenic activities, is in phase I/ II clinical trials for breast cancer. 2ME2 inhibits microtubule polymerization and causes cells to arrest in G 2 -M. The purpose of this study was to further elucidate the molecular mechanism of 2ME2. MDA-MB-435 breast cancer cells were treated with 2ME2
Objective Left ventricular hypertrophy (LVH) is a highly prevalent and robust predictor of cardiovascular morbidity and mortality. Existing studies have finely detailed mechanisms involved with its development, yet clinical translation of these findings remains unsatisfactory. We propose an alternative strategy focusing on mechanisms of LVH regression rather than its progression and hypothesize that LVH regression is associated with a distinct genomic profile Methods Minimally-invasive transverse arch banding and debanding (or their respective sham procedures) were performed in C57Bl6 male mice. LVH was assessed physiologically by transthoracic echocardiography, structurally by histology, and molecularly by real-time PCR. Mouse hearts were genomically analyzed with Agilent mouse 44k developmental gene chips. Results Compared to controls, animals banded for 28 days developed a robust hypertrophic response by heart weight/body weight ratio, histology, echocardiography, and fetal gene expression. These parameters were reversed within 1 week of debanding. Whole genome arrays on LV tissue revealed 288 genes differentially expressed during progression, 265 genes differentially expressed with regression, and only 23 genes shared by both processes. Signaling-related expression patterns were more prevalent with regression rather than the structural-related patterns associated with LVH progression. In addition, regressed hearts showed comparatively more changes in energy metabolism and protein production. Conclusions This study demonstrates an effective model for characterizing LVH and reveals that regression is genomically distinct from its development. Further examination of these expression profiles will broaden our understanding of LVH and provide a novel therapeutic paradigm focused on promoting regression of LVH, not just halting its progression.
BACKGROUND Premenopausal women represent approximately 35% of new breast cancer diagnoses. Diagnosis and treatment may lead to substantial disruption in quality of life (QOL). METHODS Premenopausal patients (aged 18 to 50 years) treated for nonmetastatic breast cancer completed a mailed questionnaire. Multiple self-reported QOL measures and clinical data were collected. Cluster analysis and Cronbach’s α were used to validate the survey. Analysis of variance was performed for specific interventions. Lower interference scores conveyed higher QOL. RESULTS The response rate was 49.8%. Cronbach’s α was 0.96. Immediate contralateral prophylactic mastectomy (CPM) carried the highest interference (mean, 3.3148) with sexuality compared with no CPM (mean, 2.85) or delayed CPM (P = .03). Breast conservation had the least interference with appearance (P < .01) and work and finances (P = .02). CONCLUSIONS Therapeutic mastectomy and CPM with or without reconstruction may adversely affect QOL. These findings suggest that the choice and timing of interventions may significantly affect patient satisfaction.
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