ABSTRACT
Microarray analysis of complementary DNA (cDNA) allows large-scale, comparative, gene expression profiling of two different cell populations. This approach has the potential for elucidating the primary transcription events and genetic cascades responsible for increased glioma cell motility in vitro and invasion in vivo. These genetic determinants could become therapeutic targets. We compared cDNA populations of a glioma cell line (G112) exposed or not to a motility-inducing substrate of cell-derived extracellular matrix (ECM) proteins using two sets of cDNA microarrays of 5,700 and 7,000 gene sequences. The data were analyzed considering the level and consistency of differential expression (outliers) and whether genes involved in pathways of motility, apoptosis, and proliferation were differentially expressed when the motility behavior was engaged. Validation of differential expression of selected genes was performed on additional cell lines and human glioblastoma tissue using quantitative RT-PCR. Some genes involved in cell motility, like tenascin C, neuropilin 2, GAP43, PARG1 (an inhibitor of Rho), PLCy, and CD44, were over expressed; other genes, like adducin 3y and integrins, were down regulated in migrating cells. Many key cell cycle components, like cyclin A and B, and proliferation markers, like PCNA, were strongly down regulated on ECM. Interestingly, genes involved in apoptotic cascades, like Bcl-2 and effector caspases, were differentially expressed, suggesting the global down regulation of proapoptotic components in cells exposed to cell-derived ECM. Overall, our findings indicate a reduced proliferative and apoptotic activity of migrating cells. cDNA microarray analysis has the potential for uncovering genes linking the phenotypic aspects of motility, proliferation, and apoptosis.
Subject(s)
Brain Neoplasms/pathology , Gene Expression Regulation, Neoplastic , Glioma/pathology , Neoplasm Invasiveness/genetics , Neoplasm Proteins/biosynthesis , Transcription, Genetic , Apoptosis/genetics , Brain Neoplasms/chemistry , Cell Cycle Proteins/biosynthesis , Cell Cycle Proteins/genetics , Cell Movement/drug effects , Cell Movement/genetics , Computer Systems , Culture Media/pharmacology , DNA, Complementary/genetics , Expressed Sequence Tags , Extracellular Matrix Proteins/pharmacology , Gene Expression Profiling , Gene Expression Regulation, Neoplastic/drug effects , Glioblastoma/chemistry , Glioblastoma/pathology , Growth Substances/biosynthesis , Growth Substances/genetics , Humans , Lasers , Neoplasm Proteins/genetics , Oligonucleotide Array Sequence Analysis , Phenotype , Polymerase Chain Reaction , Tenascin/biosynthesis , Tenascin/genetics , Transcription, Genetic/drug effects , Tumor Cells, Cultured/drug effects , Tumor Cells, Cultured/metabolism , Tumor Cells, Cultured/pathologyABSTRACT
Management of the medially deviated and overlapping second digit is often frustrating because of inconsistent surgical results. After a review of the pertinent anatomy and previous forms of treatment, both conservative and surgical, the author discusses the concept of a laterally closing metatarsal head osteotomy. Experience over the past 7 years has shown this procedure to be very effective as an adjunctive procedure in the surgical correction of the deformity.
Subject(s)
Foot Deformities/surgery , Metatarsal Bones/surgery , Metatarsophalangeal Joint/surgery , Osteotomy/methods , Toes/surgery , Female , Humans , Male , Metatarsophalangeal Joint/anatomy & histology , Postoperative ComplicationsABSTRACT
The author presents an overview of tendon healing with particular attention to the principles of tendon graft repair. A clinical case of a patient who experienced an extensor hallucis longus laceration 8 weeks prior to the graft repair is reviewed. The extensor hallucis longus tendon was repaired using an autogenous graft taken from the extensor hallucis brevis.
