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Aberrant Gene Expression (aberrant + gene_expression)
Selected AbstractsNeural precursor cells from a fatal human motoneuron disease differentiate despite aberrant gene expressionDEVELOPMENTAL NEUROBIOLOGY, Issue 3 2007Niklas Pakkasjärvi Abstract Precursor cells of the human central nervous system can be cultured in vitro to reveal pathogenesis of diseases or developmental disorders. Here, we have studied the biology of neural precursor cells (NPCs) from patients of lethal congenital contracture syndrome (LCCS), a severe motoneuron disease leading to prenatal death before the 32nd gestational week. LCCS fetuses are immobile because of a motoneuron defect, seen as degeneration of the anterior horn and descending tracts of the developing spinal cord. The genetic defect for the syndrome is unknown. We show that NPCs isolated postmortem from LCCS fetuses grow and are maintained in culture, but display increased cell cycle activity. Global transcript analysis of undifferentiated LCCS precursor cells present with changes in EGF-related signaling when compared with healthy age-matched human controls. Further, we show that LCCS-derived NPCs differentiate into cells of neuronal and glial lineage and that the initial differentiation is not accompanied by overt apoptosis. Cells expressing markers Islet-1 and Hb9 are also generated from the LCCS NPCs, suggesting that the pathogenic mechanism of LCCS does not directly affect the differentiation capacity or survival of the cells, but the absence of motoneurons in LCCS may be caused by a noncell autonomous mechanism. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007 [source] Global gene expression analysis of bovine somatic cell nuclear transfer blastocysts and cotyledonsMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 5 2009K.I. Aston Low developmental competence of bovine somatic cell nuclear transfer (SCNT) embryos is a universal problem. Abnormal placentation has been commonly reported in SCNT pregnancies from a number of species. The present study employed Affymetrix bovine expression microarrays to examine global gene expression patterns of SCNT and in vivo produced (AI) blastocysts as well as cotyledons from day-70 SCNT and AI pregnancies. SCNT and AI embryos and cotyledons were analyzed for differential expression. Also in an attempt to establish a link between abnormal gene expression patterns in early embryos and cotyledons, differentially expressed genes were compared between the two studies. Microarray analysis yielded a list of 28 genes differentially expressed between SCNT and AI blastocysts and 19 differentially expressed cotyledon genes. None of the differentially expressed genes were common to both groups, although major histocompatibility complex I (MHCI) was significant in the embryo data and approached significance in the cotyledon data. This is the first study to report global gene expression patterns in bovine AI and SCNT cotyledons. The embryonic gene expression data reported here adds to a growing body of data that indicates the common occurrence of aberrant gene expression in early SCNT embryos. Mol. Reprod. Dev. 76: 471,482, 2009. © 2008 Wiley-Liss, Inc. [source] Microarray analysis of aberrant gene expression in actinic keratosis: effect of the Toll-like receptor-7 agonist imiquimodBRITISH JOURNAL OF DERMATOLOGY, Issue 6 2007A. Torres Summary Background, The molecular events leading to actinic keratosis (AK) are not well understood. Objective, To identify and compare gene expression changes in AK lesions and in sun-exposed nonlesional skin and to determine the effect of imiquimod 5% cream on these changes. Method, A double-blind, vehicle-controlled, randomized study was conducted to evaluate the molecular changes in AK treated with imiquimod. Seventeen male subjects with , 5 AK lesions on the scalp applied vehicle or imiquimod three times a week for 4 weeks. Gene expression analysis using Affymetrix® oligonucleotide arrays was performed on shave biopsies of lesions taken before and after treatment. Confocal microscopy was performed on the study area as an adjunctive diagnostic procedure. Results, We identified gene expression changes which occur in sun-exposed, nonlesional skin as well as in AK lesions. These changes include, but are not limited to, the overexpression of oncogenic and proliferative genes and diminished expression of tumour suppressor genes. The gene expression changes observed in AK lesions and in sun-exposed, nonlesional skin were consistent with the confocal microscopy observations, which showed abnormalities in the sun-exposed, nonlesional skin, similar in nature but less pronounced than abnormalities seen in AK. Imiquimod partially or totally reversed the aberrant expression of some of the genes observed in AK, consistent with clearing of lesions and normalization of confocal cellular images. Conclusions, The data show that profound gene expression changes occur in sun-exposed, nonlesional skin which progress further in AK lesions. The data also suggest that imiquimod may play a role in normalizing gene expression and cellular morphology in sun-damaged skin. [source] Overexpression of osteopontin is associated with intrahepatic metastasis, early recurrence, and poorer prognosis of surgically resected hepatocellular carcinomaCANCER, Issue 1 2003Hung-Wei Pan M.S. Abstract BACKGROUND Intrahepatic metastasis via portal vein spread is an important feature and a crucial unfavorable prognostic factor of hepatocellular carcinoma (HCC). To identify the molecular factors for tumor progression, the authors used differential display (DD) to analyze aberrant gene expression in HCC. The goal of the current study was to elucidate the clinicopathologic and prognostic significance of osteopontin (OPN) in HCC progression. METHODS OPN mRNA levels, which were increased preferentially in HCC in a DD assay and verified with Northern blotting, were measured in 240 surgically removed, unifocal, primary HCCs using the reverse transcription,polymerase chain reaction at the exponential phase. OPN mRNA expression was correlated with clinicopathologic features, particularly portal vein invasion, early tumor recurrence, and prognosis. RESULTS Osteopontin mRNA was overexpressed in 133 tumors (55%). The OPN overexpression was associated closely with ,-fetoprotein elevation (P = 0.001), p53 mutation (P = 0.021), larger tumors (P = 0.002), high-grade HCC (P < 0.001), late-stage HCC (P < 0.001), early tumor recurrence and/or metastasis (P = 0.003), and a lower 10-year survival rate (P = 0.00013). Multivariate analysis revealed that tumor stage and early tumor recurrence were crucial prognostic factors. In early-stage HCC, which has no vascular invasion and a lower early tumor recurrence than late-stage HCC, OPN mRNA overexpression predicted a higher early recurrence rate (P = 0.003). CONCLUSIONS OPN mRNA overexpression was correlated closely with high-grade, late-stage, and early tumor recurrence, which lead to poorer prognosis. Osteopontin overexpression might serve as an unfavorable prognostic factor and a useful marker for predicting early recurrence in early-stage HCC. Cancer 2003;98:119,27. © 2003 American Cancer Society. DOI 10.1002/cncr.11487 [source] | |||||||||||||