View clinical trials related to Lymphoma Diffuse Large B-cell.
Filter by:Lymphomagenesis is partially known, and some risk factor are identified like those inducing immune deficiencies: chronic exposure to HIV, immune suppressor therapies or commun variable immunodeficiency. Parts of the mechanisms leading to NHL development after pesticide exposure are the disruption of immune surveillance against cancer cell. Pro-oncogenic action of metabolites is the most important mechanisms of action for pesticides. Thus, pesticides are metabolized in pro-oxidant compounds disturbing the redox homeostasis in the haematopoietic and immune cells precursors, promoting proliferation and survival, and inducing DNA breaks. Some of them induce direct DNA breaks and non-conform reparation, leading to activation of oncogenes; and other induces transcription factors for oncogenic signalling pathways. DNA reparation and adaptation to a higher ROS level are associated with resistance against cytotoxic chemotherapy treatment with induction of detoxification mechanism by tumour cells. That DNA repair pathways, which are targeted by chemotherapy could also explain a part of chemo-resistance. It was therefore suggested that DLBCL dependence to specific DNA repair pathways could be targeted to hamper repair of intrinsic DNA damage occurring during B-lymphoma cells proliferation or to increase DNA damage induced by chemotherapy.
The link between the products of synthetic chemistry and cancer is at the heart of much research. Recent work has identified the use of plant protection agents by farmers as a risk factor for developing non-Hodgkin lymphoma, including diffuse large B cell lymphoma (DLBCL) is the most common histology. Different biological models were used to understand the role of pesticides in lymphomagenesis. To summarize, most pesticides act at the cellular and molecular level, on different signaling pathways. After metabolized by cytochrome P450, these compounds generally become pro-oxidants. The increase in reactive oxygen species rate (SAR) causes the activation of signaling pathways involved in cell proliferation and survival. But deregulation of oxidative status does not in itself justify the specificity of the impact of pesticides on specific pathologies. Several agents have a genotoxic effect, others induce the activation of signaling pathways by binding to transcription factors and others have immunomodulating properties.
This study is sponsored by Sierra Oncology, Inc. formerly ProNAi Therapeutics, Inc. It is a multi-center, nonrandomized, open label, phase II investigation of PNT2258 to characterize anti-tumor activity and collect safety data on patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma.