A phase II study for Tegafur, Gimeracil and Oteracil potassium with or without Thalidomide for heavily treated colorectal cancer patients
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Cancer
PROVIDER: 2683960 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Thalidomide Exerts Distinct Molecular Antileukemic Effects and Combined Thalidomide/Fludarabine Therapy is Clinically Effective in High-Risk Chronic Lymphocytic Leukemia Background: Thalidomide represents a promising immunomodulatory drug that targets both leukemia cells and the tumor microenvironment. Methods: We treated chronic lymphocytic leukemia (CLL) patients with a combined thalidomide/fludarabine regimen and monitored cellular and molecular changes induced by thalidomide in-vivo prior to fludarabine treatment. Thalidomide was given daily (100mg p.o./day) and fludarabine was administered on days 7-11 (25 mg/m² i.v./day) within each 4-week cycle (maximum of 6 cycles). Twenty patients received thalidomide/fludarabine as first line therapy and 20 patients were previously treated. Unmutated IgVH mutation status was found in 36 cases and 13 had high-risk cytogenetic aberrations (deletion of 17p13 or 11q22-q23). Results: The overall response rate was 80% and 25% for untreated and previously treated patients, respectively. While thalidomide effectively reduced the number of CLL cells, the number of CD3 lymphocytes showed no significant change, but the number of CD4+CD25hiFOXP3+ T-regulatory cells was significantly decreased. Gene expression profiling revealed a thalidomide induced signature containing both targets known to play a role in immunomodulatory drug action as well as novel candidate genes. Conclusions: Combined thalidomide/fludarabine therapy demonstrated efficacy in high-risk CLL patients. Furthermore, our study provides novel biological insights into thalidomide effect, which might act by enhancing apoptosis of CLL cells and reducing Tregs, thereby enabling T-cell dependent anti-tumor effect.
2009-08-21 | GSE15913 | GEO
Project description:Colorectal cancer is a major health problem in Western society contributing to a high mortality rate. Treatment options for the majority of patients with metastases are limited to cytotoxic chemotherapies. The first line chemotherapy containing with oxaliplatin is recommend by guideline. The use of antiangiogenic agents, either alone or in combination with other therapies may provide an alternative treatment modality in the management of these patients. Metronomic chemotherapy refers to the close, regular administration of a chemotherapeutic drug, over prolonged periods. The advantages of metronomic chemotherapy include reducing acute toxicities and sometimes surprisingly good activity against drug resistant tumors via antiangiogenic effect.
Thalidomide is an agent, which has shown potential in the treatment of hematological and solid tissue malignancies such as multiple myeloma via antiangiogenic mechanism. Tegafur/uracil (UFUR) is one of the effective chemotherapeutics reported to be an effective antiangiogenic agent in an animal model of metastatic colorectal cancers (CRCs).
In the present study, the investigators will try to use low dose metronomic schedule of thalidomide with tegafur/uracil regimen to see the anti tumor efficacy in recurrent and metastasis colorectal cancer patients after oxaliplatin-contained chemotherapy.
The primary endpoints are overall response rate and clinical benefit and the secondary endpoint were to determine the progression free survival, and duration of objective response, the overall survival (OS) and to assess the safety profile. This is a prospective phase II study. After having checked all eligibility criteria, patients will be treated with Tegafur/Uracil (TU) regimen. About 34 patients will be enrolled.
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Project description:To unravel the mechanisms of thalidomide developmental toxicity, we used microarrays to study transcriptomic changes induced by thalidomide during mouse embryonic stem cell (mESC) differentiation. C57BL/6 mESCs were allowed to differentiate spontaneously and global gene expression changes were studied using microarrays at at different time points after exposure to 0.25 mM thalidomide (THD).
2015-05-31 | GSE61306 | GEO
Project description:Purpose: The aim of this study was to compare the differentially expressed genes under thalidomide treatment in limb buds. Methods: The trancriptome sequencing was performed using Illumina HiSeq 2500 ® platform. The sequence reads were aligned to the reference genome of chicken (Galgal4) downloaded from Ensembl Release 81 database. Alignment was performed using STAR (version 2.4.2a ). Expression estimation carried out using cufflinks program (version 2.2.1).Differential expression analysis carried using the cuffdiff program in cufflinks(version 2.2.1). Heat maps were generated for gene expression analysis using R statistical software.
2021-12-01 | GSE80309 | GEO
Project description:In this research, we use DNA microarray analysis to clarify the gene expression responses from thalidomide in PBMC cells after lipopolysaccharide (LPS) treatment.
2011-09-30 | GSE28708 | GEO
Project description:Comparison of gene expression data from thalidomide modulated- and unmodulated-MSCs from patients with idiopathic thrombocytopenic purpura (ITP).
2013-03-12 | GSE44948 | GEO
Project description:Purpose: The aim of this study is to analyse and compare the differentially expressed genes between nitric oxide treated and thalidomide treated chick embryos Methods: The trancriptome sequencing was performed using Illumina HiSeq 2500 ® platform. The sequence reads were aligned to the reference genome of chicken (Galgal4) downloaded from Ensembl Release 75 database. Alignment was performed using TopHat (v2.0.8) program to the Ensembl Release 75 gene model of chicken with default parameter settings. After alignment, Cuffdiff (v2.2.0) program was used for performing differential expression analysis. Pathway analysis of differentially expressed genes was performed using DAVID program. Heat maps were constructed using R package software 3.1.0.
2017-01-01 | GSE69159 | GEO
Project description:The cell differentiation potential of 13-cis retinoic acid (RA) has not succeeded in the clinical treatment of glioblastoma (GBM) so far. However, RA may also induce the expression of disistance genes such as HOXB7 which can be suppressed by Thalidomide (THAL). Therefore, we tested if combined treatment with RA+THAL may inhibit growth of glioblastoma in vivo. Treatment with RA+THAL but not RA or THAL alone significantly inhibited tumour growth. The synergistic effect of RA and THAL was corroborated by the effect on proliferation of glioblastoma cell lines in vitro. HOXB7 was not upregulated but microarray analysis validated by real-time PCR identified four potential resistance genes (IL-8, HILDPA, IGFBPA, and ANGPTL4) whose upregulation by RA was suppressed by THAL. Furthermore, genes coding for small nucleolar RNAs (snoRNA) were identified as a target for RA for the first time, and their upregulation was maintained after combined treatment. Pathway analysis showed upregulation of the Ribosome pathway and downregulation of pathways associated with proliferation and inflammation. Combined treatment with RA + THAL delayed growth of GBM xenografts and suppressed putative resistance genes associated with hypoxia and angiogenesis. This encourages further pre-clinical and clinical studies of this drug combination in GBM. The purpose was to study differential gene expression in glioblastoma xenografts after treatment with 13-cis retinoic acid (RA), thalidomide (Thal) or a combination of both drugs.
2015-07-23 | E-GEOD-71224 | biostudies-arrayexpress
Project description:Acute inflammatory episodes are common in leprosy and complicate the course of the disease. Among these episodes, Erythema Nodosum Leprosum (ENL) is more common in multibacillary patients and can cause more systemic symptoms like fever, myalgia, edema, and pain. Today, ENL is managed with thalidomide and corticosteroids, yet the exact mechanisms behind ENL remain elusive and with few pharmacological options available. In this experiment, RNA was sequenced and gene expression was measured from the blood of multibacillary patients with and without ENL in a mixed design, comparing ENL to MB and ENL before and after thalidomide treatment for 7 days.
2022-03-14 | GSE198609 | GEO
Project description:Frequently used to treat morning sickness, the drug thalidomide led to the birth of thousands of children with severe birth defects. Despite their teratogenicity, thalidomide and related IMiD drugs are now a mainstay of cancer treatment, however, the molecular basis underlying the pleiotropic biology and characteristic birth defects remains unknown. Here we show that IMiDs disrupt a broad transcriptional network through induced degradation of several C2H2 zinc finger transcription factors, including SALL4, a member of the Spalt-like family of developmental transcription factors. Strikingly, heterozygous loss of function mutations in SALL4 result in a human developmental condition that phenocopies thalidomide induced birth defects such as absence of thumbs, phocomelia, defects in ear and eye development, and congenital heart disease. We find that thalidomide induces degradation of SALL4 exclusively in humans, primates and rabbits, but not in rodents or fish, providing a mechanistic link for the species-specific pathogenesis of thalidomide syndrome.
2018-08-09 | PXD010417 | Pride