Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human sensitive and resistant tumours identify gene expression patterns in primary breast-cancer specimens that might predict response to taxanes.

ABSTRACT: These patients proved resistant to docetaxel treatment, exhibiting residual tumor of 25% or greater remaining volume.

ORGANISM(S): Homo sapiens

SUBMITTER: Eric Wooten

PROVIDER: E-GEOD-349 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Publications

Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer.

Chang Jenny C JC Wooten Eric C EC Tsimelzon Anna A Hilsenbeck Susan G SG Gutierrez M Carolina MC Elledge Richard R Mohsin Syed S Osborne C Kent CK Chamness Gary C GC Allred D Craig DC O'Connell Peter P

Lancet (London, England) 20030801 9381

<h4>Background</h4>Systemic chemotherapy for operable breast cancer substantially decreases the risk of death. Patients often have de novo resistance or incomplete response to docetaxel, one of the most active agents in this disease. We postulated that gene expression profiles of the primary breast cancer can predict the response to docetaxel.<h4>Methods</h4>We took core biopsy samples from primary breast tumours in 24 patients before treatment and then assessed tumour response to neoadjuvant do ...[more]

PMID: 12907009

Similar Datasets

Project description:We compared gene expression profiles from six donor kidneys prior to surgical manipulation to six kidneys removed after laparoscopic donor nephrectomy (LDN) and several hours of CO2 pneumoperitoneum. Biopsies were obtained from renal cortex and hybridized to Affymetrix HG-U133A GeneChips. For control kidneys we identified 1380 genes present on all 6 samples that had a signal intensity greater than 1000. Functional classification of these revealed genes for cellular signaling (201; 15%), regulation of transcription (156; 11%), cellular transport (144; 10%) and cellular metabolism (111; 8%). A class comparison between the controls and LDN kidneys yielded 865 differentially expressed genes. Functional classification of the 502 genes differentially up-regulated in LDN kidneys identified associations with apoptosis, cell adhesion, cell signaling, regulation of cell growth/proliferation, immune/inflammation, ischemia/stress response and proteolysis/peptidolysis. These data demonstrate an altered renal transcriptome induced by several hours of CO2 pneumoperitoneum and laparoscopic surgery characterized by up-regulation of ischemia and injury associated genes. Keywords: Comparative Expression Twelve healthy adult kidney donors signed a consent form, and were approved for donation according to the usual evaluation and practice of the Cleveland Clinic Renal Transplant Program. To avoid potentially significant differences in gene expression based on race and/or ethnicity, only white recipients were selected. The patients were divided into two groups; six controls from open donor nephrectomy and six from LDN. Demographic information included age, gender, race, HLA type, and renal function data including serum creatinine (mg/dL), GFR measured by iothalamate clearance (cc/min.), and urine protein excretion (mg/24 hr). Each patient was given general anesthesia and had a diuresis induced with saline, mannitol, and furosemide. The controls had an extraperitoneal flank incision made, and with only minimal manipulation of the kidney two subcapsular core renal biopsies were obtained using a 15-gauge spring-loaded needle. For the LDN cases two core renal biopsies were obtained using the same needles after the kidneys underwent 2 to 3 hours of C02 pneumoperitoneum. Study biopsies went immediately into 1.5 mL of RNALater (Ambion, Austin, TX), and were stored at –80 0C until they were processed. Biopsy specimens were homogenized in 1 mL of Trizol (Invitrogen, Carlsbad, CA); total RNA was purified using an RNeasy column (Qiagen, Valencia, CA); and quality confirmed with an Agilent 2100 BioAnalyzer (Palo Alto, CA). Standard Affymetrix GeneChip (Santa Clara, CA) protocols were used, and labelled samples were hybridized to HG-U133A GeneChip arrays containing 22,283 probe sets representing over 14,500 human genes. Data was analyzed using Signal intensities generated using GeneChip Operating System version 1.0 and were subsequently analysed by Robust Multichip Average Express (RMA Express) using all Affymetrix .CEL files as a training set. BRB ArrayTools (http://linus.nci.nih.gov/BRB-ArrayTools.html) was used to perform class comparisons (significance level of p < 0.005), and create dendrograms. We used NetAffyx (www.affymetrix.com) to annotate the differentially expressed genes according to biological function based on the Gene Ontology database. A Heatmap was created using Cluster and TreeView software. This dataset is part of the TransQST collection.

Project description:We previously observed reduced graft survival for kidney transplants having interstitial fibrosis with subclinical inflammation, but not fibrosis alone, on 1-year protocol biopsy. The current study aimed to determine whether fibrosis with inflammation at 1 year is associated with renal functional decline in a low-risk transplant cohort and to characterize the nature of the inflammation. Subjects were living-donor, tacrolimus/mycophenolate-treated transplant recipients without overt risk factors for reduced graft survival (n=151). Transplants with normal histology (n=86) or fibrosis alone (n=45) on 1-year protocol biopsy had stable renal function between 1 and 5 years, while those having fibrosis with inflammation (n=20) had declining glomerular filtration rate and reduced graft survival. Immunohistochemistry confirmed increased interstitial T-cells and macrophages/dendritic cells in the fibrosis with inflammation group. Gene expression was performed on a subset of biopsies in each group and demonstrated increased expression of transcripts related to innate and cognate immunity in transplants having fibrosis with inflammation. Pathway- and pathological process-specific analyses of microarray profiles revealed that, in fibrosis with inflammation, over-expressed transcripts were enriched for potentially damaging immunological activities including Toll-like receptor signaling, antigen presentation/dendritic cell maturation, interferon gamma-inducible response, cytotoxic T lymphocyte-associated and acute rejection-associated genes. Thus, fibrosis with inflammation in 1-year protocol biopsies is associated with reduced graft survival and function and with a rejection-like gene expression signature even in recipients with no clinical risk for inferior outcome. Early interventions aimed at altering rejection-like inflammation may favor improved long-term KTx survival. We analyzed gene expression from a group of 65 renal transplant recipients. Patient groups were carefully selected to include patients on the same immunosuppression (Prograf-MMF-Pred), transplant type (LD), absence of over post-transplant complications (AR, BK, DGF). For each patient a 1 year protocol biopsy was examined by conventional histology and gene expression. By histology the patients were categorized as histologically normal (n=25, i/cg/ci=0), IF/TA (n=24, i/cg=0, ci>0) and IFTA+i (n=16, cg=0, i/ci>0). This dataset is part of the TransQST collection.

Project description:Gene Expression Profiling of Breast Cancer Patients with Brain Metastases Brain metastases confer the worst prognosis of breast cancer as no therapy exists that prevents or eliminates the cancer from spreading to the brain. We developed a new computational modeling method to derive specific downstream signaling pathways that reveal unknown target-disease connections and new mechanisms for specific cancer subtypes. The model enables us to reposition drugs based on available gene expression data of patients. We applied this model to repurpose known or shelved drugs for brain, lung, and bone metastases of breast cancer with the hypothesis that cancer subtypes have their own specific signaling mechanisms. To test the hypothesis, we addressed the specific CSBs for each metastasis that satisfy that (1) CSB proteins are activated by the maximal number of enriched signaling pathways specific to this metastasis, and (2) CSB proteins involve in the most differential expressed coding-genes specific to the specific breast cancer metastasis. The identified signaling networks for the three types of metastases contain 31, 15, and 18 proteins, respectively, and are used to reposition 15, 9, and 2 drug candidates for the brain, lung, and bone metastases of breast cancer. We performed in vitro and in vivo preclinical experiments as well as analysis on patient tumor specimens to evaluate the targets and repositioned drugs. Two known drugs, Sunitinib (FDA approved for renal cell carcinoma and imatinib-resistant gastrointestinal stromal tumor) and Dasatinib (FDA approved for chronic myelogenous leukemia (CML) after imatinib treatment and Philadelphia chromosome-positive acute lymphoblastic leukemia), were shown to prohibit the metastatic colonization in brain. The TMH-52 cohort includes 11 patients who were examined with brain metastasis at the time of breast cancer diagnosis. The other 41 patients were examined with other organ metastasis at the time of breast cancer diagnosis.

Dataset Information

Transcription profiling of human sensitive and resistant tumours identify gene expression patterns in primary breast-cancer specimens that might predict response to taxanes.

Publications

Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets