The Effects of Eicosapentaenoic Acid (EPA) on Biomarkers of Growth and Vascularity in Human Colorectal Cancer Liver Metastases (The EPA for Metastasis Trial)

Eicosapentaenoic acid (EPA) is a naturally occuring omega-3 polyunsaturated fatty acid found in oily fish. EPA has anti-colorectal (bowel) cancer activity in experimental models. This trial will test whether EPA reduces markers of tumour growth, and is safe and well tolerated,in patients with colorectal cancer liver metastases awaiting surgery.

Start Date01 Apr 2010

Sponsor / Collaborator

University of Leeds

100 Clinical Results associated with TP-252

100 Translational Medicine associated with TP-252

100 Patents (Medical) associated with TP-252

Literatures (Medical) associated with TP-252

01 Dec 2024·Expert Opinion on Investigational Drugs

Drugs stimulating insulin secretion in early clinical development for the treatment of type 1 diabetes: what’s new?

Review

Author: Ning, Xinyuan ; Davis, Stephen N. ; Munir, Kashif M.

INTRODUCTIONType 1 diabetes is a chronic autoimmune condition characterized by the selective destruction of insulin-producing beta cells in the pancreas. The etiology of T1D is multifactorial, with a combination of genetic susceptibility and environmental triggers believed to underlie beta-cell destruction. Preserving and prolonging beta-cell function in T1D is a pivotal therapeutic objective that can mitigate disease progression and improve glycemic control.AREAS COVEREDInsulin secretagogues have long been used in the management of type 2 diabetes, but do not have a significant beneficial effect in individuals with long-standing type 1 diabetes. Enhancement of beta-cell function early in the course of type 1 diabetes may offer important benefits in glycemic control and reduced hypoglycemia risk. Glucagon-like peptide-1 receptor agonists, glucokinase activators, free fatty acid receptor agonists, and glimins are drug classes which may offer benefit in enhancing insulin secretion in individuals with type 1 diabetes.EXPERT OPINIONDrugs which enhance insulin secretion in individuals may offer clinical benefits to individuals with type 1 diabetes. However, the lack of beta-cell capacity introduces a challenge without regeneration of insulin-producing cells. Stem cell therapies combined with regulation of islet autoimmunity may offer the best prospect of increased insulin secretion in individuals with T1D.

01 Nov 2023·Brain Communications

α-Synuclein expression in response to bacterial ligands and metabolites in gut enteroendocrine cells: an in vitro proof of concept study

Article

Author: Bates, Rachel ; Gegg, Matthew E ; Schapira, Anthony H V ; Koletsi, Sofia ; Chau, Kai-Yin ; Menozzi, Elisa ; Macnaughtan, Jane ; Blottière, Hervé M ; Hurley, Michael J

AbstractCaudo-rostral migration of pathological forms of α-synuclein from the gut to the brain is proposed as an early feature in Parkinson’s disease pathogenesis, but the underlying mechanisms remain unknown. Intestinal epithelial enteroendocrine cells sense and respond to numerous luminal signals, including bacterial factors, and transmit this information to the brain via the enteric nervous system and vagus nerve. There is evidence that gut bacteria composition and their metabolites change in Parkinson’s disease patients, and these alterations can trigger α-synuclein pathology in animal models of the disorder. Here, we investigated the effect of toll-like receptor and free fatty acid receptor agonists on the intracellular level of α-synuclein and its release using mouse secretin tumour cell line 1 enteroendocrine cells. Secretin tumour cell line 1 enteroendocrine cells were treated for 24 or 48 h with toll-like receptor agonists (toll-like receptor 4 selective lipopolysaccharide; toll-like receptor 2 selective Pam3CysSerLys4) and the free fatty acid receptor 2/3 agonists butyrate, propionate and acetate. The effect of selective receptor antagonists on the agonists’ effects after 24 hours was also investigated. The level of α-synuclein protein was measured in cell lysates and cell culture media by western blot and enzyme-linked immunosorbent assay. The level of α-synuclein and tumour necrosis factor messenger RNA was measured by quantitative reverse transcription real-time polymerase chain reaction. Stimulation of secretin tumour cell line 1 enteroendocrine cells for 24 and 48 hours with toll-like receptor and free fatty acid receptor agonists significantly increased the amount of intracellular α-synuclein and the release of α-synuclein from the cells into the culture medium. Both effects were significantly reduced by antagonists selective for each receptor. Toll-like receptor and free fatty acid receptor agonists also significantly increased tumour necrosis factor transcription, and this was effectively inhibited by corresponding antagonists. Elevated intracellular α-synuclein increases the likelihood of aggregation and conversion to toxic forms. Factors derived from bacteria induce α-synuclein accumulation in secretin tumour cell line 1 enteroendocrine cells. Here, we provide support for a mechanism by which exposure of enteroendocrine cells to specific bacterial factors found in Parkinson’s disease gut dysbiosis might facilitate accumulation of α-synuclein pathology in the gut.

01 Oct 2023·Journal of Cancer Research and Therapeutics

A free fatty acid receptor agonist inducing autophagy in HT-29 cells by downregulating the AKT/mTOR signaling pathway

Article

Author: Shahriari, Ali ; Hoveizi, Elham ; Rafienia, Behnoosh

ABSTRACTAims:GW9508, a free fatty acid receptor agonist acts in a G-coupled protein receptor 40 (GPR40)-dependent pathway. Here, we investigated the induction of stress oxidative and autophagy by GW9508 in the human colorectal cancer cell line (HT-29) and the crosstalk between autophagy and apoptotic in HT-29 cells.Methods:HT-29 was treated with GW9508 at a concentrations range of 50–500 μM in fibrin gel. Cell viability was investigated using an MTT assay. Induction of autophagy and apoptosis was assessed through Western blotting for associated proteins, acridine orange staining, MDC staining, qRT-PCR, and electron microscopy. Also, we estimated the molecular interactions between GW9805 and some markers through molecular docking.Results:GW9508 inhibited HT-29 cell proliferation, induced apoptosis, and resulted in autophagy. The induced autophagy in cells was confirmed by the observation of autophagosomes, the presence of autophagy markers, including beclin-1, LC3, AMPK, and lack expression of mTOR and AKT. Moreover, GW9508 treatment significantly increased the expression of catalase and superoxide dismutase in cells.Discussion:Our results indicated that GW9508 could induce autophagy by inhibiting the Akt/mTOR in HT-29. Hence, GW9508 is suggested as a novel anticancer reagent.

100 Deals associated with TP-252

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Adenomatous Polyposis Coli	Phase 2	US	Thetis Pharmaceuticals LLC	-
Colitis, Ulcerative	Phase 2	US	Thetis Pharmaceuticals LLC	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


UEGW2013	Not Applicable	Colitis-Associated Neoplasms	60	Eicosapentaenoic acid-free fatty acid (Standard diet)	okyddllhdv(ehgdpgvmhp) = A trend toward increased Hes1 and downregulated Hath1 was found in treated arms, while a significant increase of Nrarp was observed in the Init arm (p<0.001) vszpcjlzyl (qnvexizlsc ) View more	Positive	01 Oct 2013
				EPA-FFA 1%

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

TP-252

Overview

Basic Info

Structure/Sequence

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation