Thalidomide in Treating Patients Who Have Undergone Surgery and Chemotherapy for Cancer That Has Spread Throughout the Abdomen Due to Colorectal Cancer or Appendix Cancer
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Cancer,Colorectal Neoplasms,Carcinoma Of The Appendix
PROVIDER: 2027733 | 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:RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Hyperthermia therapy kills tumor cells by heating them to several degrees above normal body temperature. Adding chemotherapy to hyperthermia and infusing it directly into the abdomen may kill more tumor cells. Giving this treatment after surgery may kill any tumor cells that remain after surgery.
PURPOSE: This phase I trial is studying the side effects and best dose of intraperitoneal hyperthermic perfusion with oxaliplatin in treating patients with stage IV peritoneal cancer due to appendix cancer or colorectal cancer.
| 2038895 | ecrin-mdr-crc
Project description:The gastrointestinal tract may be a site of origin for α-synuclein (α-syn) pathology in idiopathic Parkinson’s disease (PD), and an abundance of aggregated α-syn has recently been demonstrated in both the healthy and PD appendix. However, the molecular changes that enable gut α-syn aggregates to contribute to the development and progression of PD remain unclear. Here, our deep-sequencing of DNA methylation changes at 521 autophagy-lysosomal pathway (ALP) genes in the human appendix and brain in PD and healthy controls indicates a pattern of widespread hypermethylation in the PD appendix that is recapitulated in the PD brain. There is significant overlap in the individual ALP genes affected across the PD appendix and brain, with lysosomal genes specifically downregulated in both regions. Healthy epigenetic aging, which involves a hypermethylation of macroautophagy and selective autophagy genes in the appendix and brain, is disrupted in both areas in PD. In mice, DNA methylation changes at ALP genes induced by chronic gut inflammation are greatly exacerbated by the presence of α-syn pathology. DNA methylation changes at ALP genes induced by α-synucleinopathy are significantly associated with the ALP abnormalities observed in the PD appendix, specifically involving lysosomal genes. Our work, which constitutes an in-depth, unbiased investigation of epigenetic changes in the ALP of the PD gut and brain, identifies the epigenetic misregulation of the ALP, especially a downregulation of lysosomal genes, as a potential culprit for the initiation and spread of α-syn pathology in idiopathic PD.
2021-03-01 | GSE135750 | GEO
Project description:The gastrointestinal tract may be a site of origin for α-synuclein (α-syn) pathology in idiopathic Parkinson’s disease (PD), and an abundance of aggregated α-syn has recently been demonstrated in both the healthy and PD appendix. However, the molecular changes that enable gut α-syn aggregates to contribute to the development and progression of PD remain unclear. Here, our deep-sequencing of DNA methylation changes at 521 autophagy-lysosomal pathway (ALP) genes in the human appendix and brain in PD and healthy controls indicates a pattern of widespread hypermethylation in the PD appendix that is recapitulated in the PD brain. There is significant overlap in the individual ALP genes affected across the PD appendix and brain, with lysosomal genes specifically downregulated in both regions. Healthy epigenetic aging, which involves a hypermethylation of macroautophagy and selective autophagy genes in the appendix and brain, is disrupted in both areas in PD. In mice, DNA methylation changes at ALP genes induced by chronic gut inflammation are greatly exacerbated by the presence of α-syn pathology. DNA methylation changes at ALP genes induced by α-synucleinopathy are significantly associated with the ALP abnormalities observed in the PD appendix, specifically involving lysosomal genes. Our work, which constitutes an in-depth, unbiased investigation of epigenetic changes in the ALP of the PD gut and brain, identifies the epigenetic misregulation of the ALP, especially a downregulation of lysosomal genes, as a potential culprit for the initiation and spread of α-syn pathology in idiopathic PD.
2021-03-01 | GSE135746 | GEO
Project description:The gastrointestinal tract may be a site of origin for α-synuclein (α-syn) pathology in idiopathic Parkinson’s disease (PD), and an abundance of aggregated α-syn has recently been demonstrated in both the healthy and PD appendix. However, the molecular changes that enable gut α-syn aggregates to contribute to the development and progression of PD remain unclear. Here, our deep-sequencing of DNA methylation changes at 521 autophagy-lysosomal pathway (ALP) genes in the human appendix and brain in PD and healthy controls indicates a pattern of widespread hypermethylation in the PD appendix that is recapitulated in the PD brain. There is significant overlap in the individual ALP genes affected across the PD appendix and brain, with lysosomal genes specifically downregulated in both regions. Healthy epigenetic aging, which involves a hypermethylation of macroautophagy and selective autophagy genes in the appendix and brain, is disrupted in both areas in PD. In mice, DNA methylation changes at ALP genes induced by chronic gut inflammation are greatly exacerbated by the presence of α-syn pathology. DNA methylation changes at ALP genes induced by α-synucleinopathy are significantly associated with the ALP abnormalities observed in the PD appendix, specifically involving lysosomal genes. Our work, which constitutes an in-depth, unbiased investigation of epigenetic changes in the ALP of the PD gut and brain, identifies the epigenetic misregulation of the ALP, especially a downregulation of lysosomal genes, as a potential culprit for the initiation and spread of α-syn pathology in idiopathic PD.
2021-03-01 | GSE135744 | GEO
Project description:The gastrointestinal tract may be a site of origin for α-synuclein (α-syn) pathology in idiopathic Parkinson’s disease (PD), and an abundance of aggregated α-syn has recently been demonstrated in both the healthy and PD appendix. However, the molecular changes that enable gut α-syn aggregates to contribute to the development and progression of PD remain unclear. Here, our deep-sequencing of DNA methylation changes at 521 autophagy-lysosomal pathway (ALP) genes in the human appendix and brain in PD and healthy controls indicates a pattern of widespread hypermethylation in the PD appendix that is recapitulated in the PD brain. There is significant overlap in the individual ALP genes affected across the PD appendix and brain, with lysosomal genes specifically downregulated in both regions. Healthy epigenetic aging, which involves a hypermethylation of macroautophagy and selective autophagy genes in the appendix and brain, is disrupted in both areas in PD. In mice, DNA methylation changes at ALP genes induced by chronic gut inflammation are greatly exacerbated by the presence of α-syn pathology. DNA methylation changes at ALP genes induced by α-synucleinopathy are significantly associated with the ALP abnormalities observed in the PD appendix, specifically involving lysosomal genes. Our work, which constitutes an in-depth, unbiased investigation of epigenetic changes in the ALP of the PD gut and brain, identifies the epigenetic misregulation of the ALP, especially a downregulation of lysosomal genes, as a potential culprit for the initiation and spread of α-syn pathology in idiopathic PD.
2021-03-01 | GSE135742 | GEO
Project description:The gastrointestinal tract may be a site of origin for α-synuclein (α-syn) pathology in idiopathic Parkinson’s disease (PD), and an abundance of aggregated α-syn has recently been demonstrated in both the healthy and PD appendix. However, the molecular changes that enable gut α-syn aggregates to contribute to the development and progression of PD remain unclear. Here, our deep-sequencing of DNA methylation changes at 521 autophagy-lysosomal pathway (ALP) genes in the human appendix and brain in PD and healthy controls indicates a pattern of widespread hypermethylation in the PD appendix that is recapitulated in the PD brain. There is significant overlap in the individual ALP genes affected across the PD appendix and brain, with lysosomal genes specifically downregulated in both regions. Healthy epigenetic aging, which involves a hypermethylation of macroautophagy and selective autophagy genes in the appendix and brain, is disrupted in both areas in PD. In mice, DNA methylation changes at ALP genes induced by chronic gut inflammation are greatly exacerbated by the presence of α-syn pathology. DNA methylation changes at ALP genes induced by α-synucleinopathy are significantly associated with the ALP abnormalities observed in the PD appendix, specifically involving lysosomal genes. Our work, which constitutes an in-depth, unbiased investigation of epigenetic changes in the ALP of the PD gut and brain, identifies the epigenetic misregulation of the ALP, especially a downregulation of lysosomal genes, as a potential culprit for the initiation and spread of α-syn pathology in idiopathic PD.
2021-02-01 | GSE135743 | GEO
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