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| Status |
Public on Jul 31, 2007 |
| Title |
Epigenetic therapy with hydralazine and magnesium valproate added to chemoradiation in cervical carcinoma. |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
As a number of epigenetic alterations have been described in cervical cancer which may participate in the development and progression of this tumor, and the primary treatment for locally advanced disease is concurrent chemoradiation, we wanted to evaluate the efficacy and safety of hydralazine and valproate added to radiation and cisplatin. In addition, the transcriptome changes induced by the epigenetic drugs were also evaluated.
Keywords: Cervical Cancer, epigenetic therapy, valproate, hydralazine, transcriptional response, epigenetic drugs
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| Overall design |
Previously untreated patients with histological diagnosis of carcinoma of the cervix and FIGO staged IIIB were entered into this phase II study. Patients received a single oral dose of 500 mg of sulphamethazine early in the morning, and urine was collected within the ensuing 6 h for phenotyping of acetylator status as reported. Afterward, patients began treatment (day –7) with a daily dose of a slow-release formulation of hydralazine tablets containing either 182 mg for rapid, or 83 mg for slow acetylators. Magnesium valproate tablets of 700 mg were also administered as a slow-release formulation at a dose of 30 mg/kg t.i.d. Both were administered until intracavitary therapy was completed. Punch biopsies were taken from primary cervical tumors at diagnosis and at day 8 of treatment with hydralazine and magnesium valproate prior to the first dose of cisplatin and external radiation. Part of the biopsy was sent to the Institution’s Pathology Department for routine hematoxilin and eosin evaluation. The remaining biopsy specimen was immediately frozen at –70°C for biological analyses.
RNA isolation was done in TRIzol according to manufacturer’s instructions. One μg of total RNA was used as input material. All reagents were provided in the CodeLink expression assay kit (Amersham, Piscataway, NJ USA). First-strand cDNA was generated using Superscript II reverse transcriptase and a T7 primer. Subsequently, second-strand cDNA was produced using E. coli DNA polymerase I and RNase H. The resultant double-stranded cDNA was purified on a QIAquick column (Qiagen, Valencia, CA) and cRNA was generated via an in vitro transcription reaction using T7 RNA polymerase and biotin-11-UTP (Perkin-Elmer, Boston, MA). cRNA was purified on an RNeasy column (Qiagen), quantified by UV spectrophotometry, and 10ug were then fragmented by heating at 94°C for 20 minutes in the presence of magnesium. The fragmented cRNA was hybridized overnight at 37°C in hybridization buffer to a CodeLink Whole Human Genome Bioarray in an Innova 4080 shaking incubator (New Brunswick, Edison, NJ) at 300 rpm.
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| Contributor(s) |
Perez-Plasencia C, Duenas-Gonzalez A |
| Citation missing |
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| Submission date |
Jul 26, 2007 |
| Last update date |
Oct 28, 2014 |
| Contact name |
Carlos Pérez-Plasencia |
| E-mail(s) |
car_plas@yahoo.com
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| Phone |
+(52) 55 56280400
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| Fax |
+(52) 55 56280486
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| URL |
http://www.incan.edu.mx/
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| Organization name |
INSTITUTO NACIONAL DE CANCEROLOGIA
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| Department |
BASIC RESEARCH
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| Lab |
EPIGENETICS
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| Street address |
Av. San Fernando 22
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| City |
México |
| State/province |
D.F. |
| ZIP/Postal code |
14080 |
| Country |
Mexico |
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| Platforms (1) |
| GPL2895 |
GE Healthcare/Amersham Biosciences CodeLink Human Whole Genome Bioarray |
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| Samples (22)
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| GSM213339 |
Cervical carcinoma 97 Pre-treatment |
| GSM213376 |
Cervical carcinoma 2 Post-treatment |
| GSM213377 |
Cervical carcinoma 2 Pre-treatment |
| GSM213384 |
Cervical carcinoma 16 Post-treatment |
| GSM213391 |
Cervical carcinoma 16 Pre-treatment |
| GSM213393 |
Cervical carcinoma 22 Pre-treatment |
| GSM213394 |
Cervical carcinoma 24 Post-treatment |
| GSM213396 |
Cervical carcinoma 22 Post-treatment |
| GSM213397 |
Cervical carcinoma 24 Pre-treatment |
| GSM213400 |
Cervical carcinoma 26 Post-treatment |
| GSM213401 |
Cervical carcinoma 26 Pre-treatment |
| GSM213407 |
Cervical carcinoma 33 Post-treatment |
| GSM213424 |
Cervical carcinoma 33 Pre-treatment |
| GSM213425 |
Cervical carcinoma 49 Post-treatment |
| GSM213427 |
Cervical carcinoma 49 Pre-treatment |
| GSM213429 |
Cervical carcinoma 63 Post-treatment |
| GSM213431 |
Cervical carcinoma 69 Post-treatment |
| GSM213434 |
Cervical carcinoma 63 Pre-treatment |
| GSM213438 |
Cervical carcinoma 69 Pre-treatment |
| GSM213444 |
Cervical carcinoma 77 Post-treatment |
| GSM213445 |
Cervical carcinoma 77 Pre-treatment |
| GSM213446 |
Cervical carcinoma 97 Post-treatment |
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| Relations |
| BioProject |
PRJNA101771 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE8604_RAW.tar |
85.6 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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