The Anti-tumour Agent, Cisplatin, and its Clinically Ineffective Isomer, Transplatin, Produce Unique Gene Expression Profiles in Human Cells

Cisplatin is a DNA-damaging anti-cancer agent that is widely used to treat a range of tumour types. Despite its clinical success, cisplatin treatment is still associated with a number of dose-limiting toxic side effects. The purpose of this study was to clarify the molecular events that are important in the anti-tumour activity of cisplatin, using gene expression profiling techniques. Currently, our incomplete understanding of this drug's mechanism of action hinders the development of more efficient and less harmful cisplatin-based chemotherapeutics. In this study the effect of cisplatin on gene expression in human foreskin fibroblasts has been investigated using human 19K oligonucleotide microarrays. In addition its clinically inactive isomer, transplatin, was also tested. Dual-fluor microarray experiments comparing treated and untreated cells were performed in quadruplicate. Cisplatin treatment was shown to significantly up- or down-regulate a consistent subset of genes. Many of these genes responded similarly to treatment with transplatin, the therapeutically inactive isomer of cisplatin. However, a smaller proportion of these transcripts underwent differential expression changes in response to the two isomers. Some of these genes may constitute part of the DNA damage response induced by cisplatin that is critical for its anti-tumour activity. Ultimately, the identification of gene expression responses unique to clinically active compounds, like cisplatin, could thus greatly benefit the design and development of improved chemotherapeutics.

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Gene Expression Profiles at Moxibustioned Site (ST36): A Microarray Analysis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/890579 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Hai-Yan Yin ◽

Yong Tang ◽

Sheng-Feng Lu ◽

Ling Luo ◽

Jia-Ping Wang ◽

...

Keyword(s):

Gene Expression ◽

Microarray Analysis ◽

Expression Profiles ◽

Alternative Therapy ◽

Gene Expression Profiles ◽

Biological Processes ◽

Physiological Conditions ◽

Pathological Conditions ◽

Molecular Events ◽

Zusanli Acupoint

As a major alternative therapy in Traditional Chinese Medicine, it has been demonstrated that moxibustion could generate a series of molecular events in blood, spleen, and brain, and so forth. However, what would happen at the moxibustioned site remained unclear. To answer this question, we performed a microarray analysis with skin tissue taken from the moxibustioned site also Zusanli acupoint (ST36) where 15-minute moxibustion stimulation was administrated. The results exhibited 145 upregulated and 72 downregulated genes which responded immediately under physiological conditions, and 255 upregulated and 243 downregulated genes under pathological conditions. Interestingly, most of the pathways and biological processes of the differentially expressed genes (DEGs) under pathological conditions get involved in immunity, while those under physiological conditions are involved in metabolism.

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Gene Expression Profiles of Early Implant Adherent Cells in Smokers and Nonsmokers

Journal of Oral Implantology ◽

10.1563/aaid-joi-d-13-00266 ◽

2015 ◽

Vol 41 (6) ◽

pp. 640-645 ◽

Cited By ~ 6

Author(s):

Ghadeer Thalji ◽

Lyndon F. Cooper ◽

Salvador Nares

Keyword(s):

Gene Expression ◽

Early Stage ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Whole Genome ◽

Adherent Cells ◽

Mini Implants ◽

Molecular Events ◽

The Impact

The objective of this study was to evaluate the impact of smoking on the early molecular events involved in peri-implant healing at either a micro-roughened or a micro-roughened with superimposed nanofeatures surface implant in humans. Twenty-one subjects, 10 smokers and 11 nonsmokers received 4 mini-implants (2.2 × 5.0 mm; 2 of each surface). After 3 and 7 days, paired mini-implants were retrieved by reverse threading and RNA isolated from implant adherent cells. Whole genome microarrays were used interrogate the gene expression profiles. The study failed to identify differences in the gene expression profiles of implant adherent cells at this early stage of osseointegration (up to day 7) comparing smoker and nonsmoker individuals.

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Validating Molecular Targets of Thalidomide in CLL: Net Effect of Increased Apoptosis through the Intrinsic Pathway and down Regulation of NF-kB Signaling- Validation Using Gene Expression Profile from the Phase I/II Clinical Trial of Thalidomide and Fludarabine.

Blood ◽

10.1182/blood.v106.11.5043.5043 ◽

2005 ◽

Vol 106 (11) ◽

pp. 5043-5043

Author(s):

Asher Alban Chanan-Khan ◽

Swaminathan Padmanabhan ◽

Leighton Stein ◽

Jennifer Panzarella ◽

Kena C. Miller ◽

...

Keyword(s):

Gene Expression ◽

B Cells ◽

Expression Analysis ◽

Clinical Success ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Molecular Targets ◽

Post Treatment ◽

Clinical Activity ◽

Base Line

Abstract Thalidomide is novel agent with demonstrated antitumor activity in various tumor types. The exact mechanism of the antineoplastic effects of thalidomide remains unknown despite its clinical success. We recently reported on the clinical activity of T in combination with F in patients with treatment naive CLL. In this clinical study pts were treated with T alone for 7 days prior to initiating F. Anti-leukemic effects of T were noted as early as day 7. To investigate the molecular targets of T in malignant CLL cells we analyzed changes in gene expression profiles at base line and at day 7-post treatment with T. Here we report on oligonucleotide microarray expression analysis of these patients, the clinical data is presented separately. Materials and methods: Peripheral blood samples from 5 patients for gene expression profiling were collected on day 0(prior to thalidomide) and on day 7 after completing thalidomide but prior to fludarabine infusion. DNA was extracted from apoptotic cells. Purified B cells extracted by Ficoll-hypaque were homogenized in Trizol and total RNA was extracted from samples prepared for GeneChip analysis as described in the Affymetrix GeneChip Expression Analysis Manual and biotinylated using Bioarray. After QC the samples were hybridized to U95A chips, representing over 12,000 annotated genes from the Unigene database. QPCR analysis was performed using ABI7900 sequence detector system. The data obtained were analyzed using Rapid Multi-Array Analysis (RMA) with all gene ontology (GO) functional annotations and chromosomal locations determined using NetAffx and Locus Link. Pathway Analysis: Two approaches were used-one using Pathway Assist Software, genes altered by Thalidomide were compared to those implicated in established pathways and second by constructing Biological Association Networks (BANS) which identifies associations to over 140,000 biological facts extracted from PubMed. Results: In each of the 5 paired samples 51 genes consistently displayed increased expression- mainly genes whose primary function were related to the immune response and apoptosis while 53 genes- mainly the signal transduction were lower. In particular the apoptotic response include mainly the intrinsic pathways and the activation of the granule mediated pathways. In the surviving B cells many of the genes were directly or indirectly related to the upregulation of nuclear factor kappa B (NF-kB) suggesting possible mechanism of resistance to thalidomide. QPCR validation using five different genes CFLAR, HBD, ILIB, TNF-a and PTPNS1 were done in additional 12 paired CLL samples. The PTPNS1 gene involved in the NF-kB signaling pathway was elevated in 8 of the post treatment samples. Conclusions: Any treatment of CLL, a malignancy with failure of apoptotic cellular machinery must be able to overcome pro-survival mechanisms and induce apoptosis. Our results show that Thalidomide induces a net effect of increasing apoptosis-related responses in malignant B cells through several distinct mechanisms and decreasing those involving the NF-kB pathway. We will present the complete gene expression data at the Annual meeting.

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Ras dexamethasone-induced protein 1 is a modulator of hormone secretion in the volume overloaded heart

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01085.2011 ◽

2012 ◽

Vol 302 (9) ◽

pp. H1826-H1837 ◽

Cited By ~ 14

Author(s):

Monica Forero McGrath ◽

Tsuneo Ogawa ◽

Adolfo J. de Bold

Keyword(s):

Gene Expression ◽

Expression Profiles ◽

Hormone Secretion ◽

Gene Expression Profiles ◽

Transcriptional Response ◽

Volume Overload ◽

Inhibitory Protein ◽

Therapeutic Implications ◽

Molecular Events

Because of the crucial role of the endocrine heart in maintaining homeostasis, considerable effort has been focused on the elucidation of the mechanistic underlying gene expression and secretion of the cardiac hormones atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP). However, much remains to be determined regarding specific molecular events involved in cardiocyte secretory function. In this work, we identified genes involved in the transcriptional response of the endocrine heart to volume overload (VO) and signaling pathways involved in its regulation. To this end, the cardiac atrial and ventricular transcriptomes were analyzed in the heart of rats subjected to experimentally induced aorto-caval shunt VO. Pathway analysis revealed unique gene expression profiles in the VO atria for G-protein signaling, notably a significant downregulation of Ras dexamethasone-induced protein 1 (RASD1). In vitro, knockdown of RASD1 in the atrial-derived HL-1 cells, significantly increased ANF secretion. Concurrent knockdown of RASD1 and its effectors Gαo1 or Gβ1γ2 abrogated the endocrine response, demonstrating a previously unknown negative modulator role for RASD1. RASD1 thus emerges as a tonic inhibitor of ANF secretion and illustrates for the first time the concept of inhibitory protein regulators of ANF release. The novel molecular function identified herein for RASD1 is of considerable importance given its therapeutic implications for cardiovascular disease.

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Genome-Wide Oligonucleotide Microarray Analysis of Gene-Expression Profiles of Taiwanese Patients with Anaplastic Astrocytoma and Glioblastoma Multiforme

CrossRef Listing of Deleted DOIs ◽

10.1177/1087057108323908 ◽

2008 ◽

Vol 13 (9) ◽

pp. 912-921 ◽

Cited By ~ 4

Author(s):

Chia-Lin Chang

Keyword(s):

Gene Expression ◽

Disease Risk ◽

Expression Profiles ◽

Laser Scanner ◽

Gene Expression Profiles ◽

Diagnostic Markers ◽

Oligonucleotide Microarray ◽

High Data ◽

Molecular Events ◽

Oligonucleotide Microarray Analysis

This study investigated the relationship between gene expression and disease based on the expression profiles of tissue-specific genes, with the aim of discovering the candidate genes associated with disease risk as diagnostic markers. The gene-expression profiles of approximately 20,000 genes from 4 anaplastic astrocytomas (AAs), 7 glioblastoma multiformes (GBMs), and 1 nontumor brain (NB) were analyzed by in situ—synthesized 60-mer oligonucleotide microarray. The signal intensity of each feature was measured by laser scanner, and gene expression was quantified as the tumor/NB intensity ratio. Gene expression was defined as having increased or decreased when the ratio was ≥1.5 or ≤ 0.67, respectively. In comparison with NB, 20 genes showed increased expression, and 32 showed decreased expression in AA, while 20 genes showed increased expression, and 164 showed decreased expression in GBM. This research indicates that changes in expression levels of 4 genes in AA and 6 genes in GBM may be useful diagnostic markers. Quantitative reverse transcription—polymerase chain reaction also supported the microarray results for the 6 selected genes. In conclusion, microarray images of excellent quality are of high data reproducibility using entirely standard procedures, and these genes may be associated with the molecular events leading to AA or GBM. ( Journal of Biomolecular Screening 2008:912-921)

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