Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genistein in Treatment of Metastatic Colorectal Cancer

ABSTRACT: Colorectal neoplasms are the third most common malignancies in the United States. Patients with metastatic (stage IV) colorectal cancer have a median life expectancy of 2 years. The response rates to chemotherapy range from 35-40%. Epidemiologic evidence suggests that soy compounds may reduce the incidence of colorectal cancers. Laboratory analyses demonstrate that genistein, a soy-derived compound, may inhibit Wnt signaling, a pathway activated in majority of colorectal cancers. Laboratory observations also demonstrate that genistein may augment growth inhibition when combined with chemotherapeutic agents of 5-Fluorouracil and platinum compounds. Based on pre-clinical data the investigators hypothesize that combining genistein with the standard of care chemotherapeutic regimens will reduce chemotherapy resistance and improve response rates in patients. The aim of the study is to add genistein to the regimens of FOLFOX or FOLFOX-Avastin in patients with newly diagnosed stage IV colon or rectal neoplasms.

DISEASE(S): Rectal Neoplasms,Colon Cancer,Colorectal Cancer,Colorectal Neoplasms,Rectal Cancer,Colonic Neoplasms

PROVIDER: 2154917 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

ACCESS DATA

Json Xml

Similar Datasets

Identification of SNP candidates associated with chemo-responsiveness in colorectal cancer patients

Project description:Response rates of 118 colorectal cancer patients to regiments were evaluated by histoculture drug response assay. Affymetrix SNP 6.0 chips were used to determine genotypes of the same colorectal cancer patients. SNPs associated with chemosensitivity to treatment regiments were identified by genome-wide association study. AV: avastin (Bevacizumab), ER: Erbitux (Cetuximab), FXA: bevacizumab + FOLFOX, FXE: Cetuximab + FOLFOX , FRA: Bevacizumab + FOLFIRI, FRE: Cetuximab + FOLFIRI; Numbers (0-100) represent responsiveness to the given drug regimens; the larger, the better responsive to given regimens

2011-03-25 | GSE21228 | GEO

Prolonged fasting times reap greater geroprotective effects when combined with caloric restriction in adult female mice

Project description:Emerging new evidence highlights the importance of prolonged daily fasting periods for the health and survival benefits of calorie restriction (CR) and time-restricted feeding (TRF) in male mice; however, little is known about the impact of these feeding regimens in females. We placed 14-month-old female mice on five different dietary regimens, either CR or TRF with different feeding windows, and determined the effects of these regimens on physiological responses, progression of neoplasms and inflammatory diseases, serum metabolite levels, and lifespan. Compared with TRF feeding, CR elicited a robust systemic response, as it relates to energetics and healthspan metrics, a unique serum metabolomics signature in overnight fasted animals, and was associated with an increase in lifespan. These results indicate that daytime (rest-phase) feeding with prolonged fasting periods initiated late in life confer greater benefits when combined with imposed lower energy intake.

2024-05-14 | MTBLS790 | MetaboLights

Single-Cell Analysis Reveals Cellular Reprogramming in Advanced Colon Cancer Following FOLFOX-Bevacizumab Treatment

Project description:The combination of FOLFOX and bevacizumab (FOLFOX-Bev) is a promising treatment for advanced colorectal cancer (CRC). To gain insights into the cellular changes associated with FOLFOX-Bev treatment, we conducted single-cell transcriptomic analysis of CRC samples derived from a patient before and after treatment. Our results show that cancer cells with high proliferative, metastatic, and pro-angiogenic properties respond better to FOLFOX-Bev treatment. Moreover, FOLFOX-Bev enhances CD8+ T cell cytotoxicity, thereby boosting the anti-tumor immune response. Conversely, FOLFOX-Bev impairs the functionality of tumor-associated macrophages, plasma cells, and cancer-associated fibroblasts, leading to a decrease in VEGFB-mediated angiogenesis. Furthermore, FOLFOX-Bev treatment reset intercellular communication, which could potentially affect the function of non-cancer cells. Our findings provide valuable insights into the molecular mechanisms underlying the response of advanced CRC to FOLFOX-Bev treatment and highlight potential targets for improving the efficacy of this treatment strategy.

2023-07-20 | GSE232525 | GEO

Optimized high-order drug mixtures improve colorectal carcinoma treatment via inactivationof MAP kinase signaling pathway and cell cycle alteration

Project description:Colorectal carcinoma is currently treated with a combination of chemotherapeutic drugs supplemented with targeted drugs. Since there is an eminent need to improved therapeutic success we employed the phenotypically-driven therapeutically guided multidrug optimization (TGMO) technology to identify personalized optimal drug combinations (ODCs). Using this technology we obtained low dose synergistic and selective ODCs for a panel of human colorectal carcinoma cells that remained active in 3-dimensional heterotypic co-culture models. From RNA sequencing and phosphoproteomics analysis we noticed considerable overlap in the top 20 most active kinases in all cell lines and that the mechanism converges around MAP kinase signaling and cell cycle inhibition despite differential cell mutation status, transcript expression levels and protein kinase activity. RNA sequencing revealed differentially expressed genes that confirmed these observations. These combinations were subsequently translated to in vivo models. Interestingly, the optimized drug mixtures reduced tumor volume with 80% and significantly outperformed the standard chemotherapy (FOLFOX) in these models, while preventing toxicity, observed after FOLFOX treatment. Pharmacokinetics studies demonstrated that the combinations supported significantly enhanced drug bioavailability.

2021-09-09 | PXD016604 | Pride

Khajanchi2015 - The combined effects of optimal control in cancer remission

Project description:The combined effects of optimal control in cancer remission SubhasKhajanchi DibakarGhosh Abstract We investigate a mathematical model depicting the nonlinear dynamics of immunogenic tumors as envisioned by Kuznetsov et al. [1]. To understand the dynamics under what circumstances the cancer cells can be eliminated, we implement the theory of optimal control. We design two types of external treatment strategies, one is Adoptive Cellular Immunotherapy and another is interleukin-2. Our aim is to establish the treatment regimens that maximize the effector cell count and minimize the tumor cell burden and the deleterious effects of the total amount of drugs. We derive the existence of an optimal control by using the boundedness of solutions. We characterize the optimality system, in which the state system is coupled with co-states. The uniqueness of an optimal control of our problem is also analyzed. Finally, we demonstrate the numerical illustrations that the optimal regimens reduce the tumor burden under different scenarios.

2024-09-02 | BIOMD0000000897 | BioModels

Phase II study of therapy selected by tumor molecular profiling in patients with previously treated metastatic pancreatic cancer. A study of the Stand Up to Cancer (SU2C) study consortium

Project description:The study accrued 49 subjects, and 48 underwent a tumor biopsy. and MP based therapy was administered to 35 patients. Study therapy was not given in 13 subjects either due to insufficient tumor on biopsy (n=8) or due to worsening cancer related symptoms after biopsy (n=5) . The demographics of evaluable patients (n=35) are M/F (59%/41%), with and age range was 34-78 (median 63 years). Time from first diagnosis of mPC to biopsy ranged from 5.8-26.7 months (median 16.1 months). Patients had 1-6 prior regimens with a median of 2. The most common IHC targets were topoisomerase 1 or 2, thymidylate synthase, ERCC1 and SPARC. Only commercially available agents were prescribed. Common regimens/agents recommended were FOLFIRI, FOLFOX, irinotecan and doxorubicin. Response rate was 9% , overall median survival of 6 months and 1 year survival was 21%.

2014-12-31 | GSE64462 | GEO

Exploring MicroRNA Patterns as Biomarkers of FOLFOX Chemotherapy-Induced Peripheral Neuropathy in Patients with Colorectal Cancer

Project description:This study aimed to identify potential miRNA-based biomarkers that can predict FOLFOX-CIPN symptoms. High throughput microRNA sequencing was performed on the RNA circulating in the plasma of eight patients with CRC who underwent FOLFOX chemotherapy. miRNA expression profiles were evaluated according to two groups: those who underwent ≤three cycles and those who underwent ≥six cycles of FOLFOX chemotherapy.

2024-03-06 | GSE260661 | GEO

Development of complete personalized treatment plans for early stage colorectal cancer patients

Project description:593 FFPE colorectal cancer samples were used to generate three prediction models: Recurrence prediction, 5FU efficacy prediction, and FOLFOX efficacy prediction The recurrence prediction study has 235 samples , 5FU efficacy prediction study has 192 samples, FOLFOX had 166 samples

2017-06-10 | GSE81653 | GEO

Identification of potential new therapeutic approaches for JAK2 V617F mutant patients

Project description:Myelofibrosis is often associated with the myeloproliferative neoplasms and expression of oncogenic JAK2 mutants. Patients with myelofibrosis have diminished quality of life due to systemic symptoms arising from fibrotic changes in the bone marrow. The introduction of the JAK2 inhibitor, ruxolitinib, has been of benefit in the treatment of myelofibrosis patients however, it is not curative and there is still a requirement for new targeted therapies to eradicate the cells at the heart of myelofibrosis pathology. Repurposing drugs bypasses many of the hurdles present in drug development, such as toxicity and pharmacodynamic profiling. To this end we undertook a re-analysis of our pre-existing proteomic data sets to identify perturbed biochemical pathways and their associated drugs/inhibitors to potentially target the cells driving myelofibrosis. This approach identified CBL0137 as a candidate for targeting JAK2 mutant driven malignancies. We therefore assessed CBL0137 as a new agent to extinguish JAK2 mutant primitive cells and show its ability to preferentially target cells from MF patients compared to healthy control cells. Further we define its mechanistic action in primary haemopoietic progenitor cells and demonstrate its ability to reduce splenomegaly and reticulocyte number in a transgenic murine model of myeloproliferative neoplasms.

2022-08-11 | E-MTAB-11653 | biostudies-arrayexpress

Inhibiting YAP1 in hepatoblastoma drives therapeutic differentiation of tumor cells to functional hepatocyte-like cells

Project description:Despite advances in surgical care and chemotherapeutic regimens, the five-year survival rate for Stage IV Hepatoblastoma (HB), the predominant pediatric liver tumor, remains at 27%. YAP1 and β-Catenin co-activation occur in 80% of children’s HB; however, a lack of conditional genetic models precludes exploration of tumor maintenance and therapeutic targets. Thus, the clinical need for a targeted therapy remains unmet. Given the predominance of YAP1 and β-catenin activation in children’s tumors, we sought to evaluate YAP1 as a therapeutic target in HB. We engineered the first conditional murine model of HB using hydrodynamic injection to deliver transposon plasmids encoding inducible YAP1S127A, constitutive β-CateninDelN90, and a luciferase reporter to murine liver. Tumor regression was evaluated using in vivo bioluminescent imaging, and tumor landscape characterized using RNA sequencing, ATAC sequencing and DNA foot-printing. Here we show that YAP1 inhibition mediates >90% tumor regression with survival for 230+ days in mice. Mechanistically, YAP1 inhibition induces a cell fate switch driving therapeutic differentiation of HB tumors into Ki-67 negative “hbHep cells” with hepatocyte-like morphology and mature hepatocyte gene expression.

2020-07-14 | GSE146548 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data