Natural product-derived PD-1 pathway blockade for Human cancer therapy: N(1), N(11)-Diethylnorspermine (DENSPM), a spermine analog, decreases the expression of Glycogen synthase kinase-3β, increases transcription factor T-bet expression, decreases the abundance of co-inhibitory receptor PD-1 on the cell surface of Cytotoxic-T-cells, increases cytotoxic T lymphocyte function and augments anti-tumor activity, via up-regulation of its target gene, 8/December/2016, 11.31 pm

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Introduction:What they say

A recent study from Cell Signalling Section, Division of Immunology, Department of Pathology, Tennis Court Road, University of Cambridge, Cambridge CB2 1QP, UK shows that “Glycogen Synthase Kinase 3 Inactivation Drives T-bet-Mediated Downregulation of Co-receptor PD-1 to Enhance CD8(+) Cytolytic T Cell Responses.” This study was published in the 16 February 2016 issue of Immunity (one of the best journals in Immunology with an impact factor of 20+) by Prof Rudd CE, Taylor A and others.


What we say

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On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Natural product-derived PD-1 pathway blockade for Human cancer therapy:  N(1), N(11)-Diethylnorspermine (DENSPM), a spermine analog, decreases the expression of Glycogen synthase kinase-3β, increases transcription factor T-bet expression, decreases the abundance of co-inhibitory receptor PD-1 on the cell surface of Cytotoxic-T-cells, increases cytotoxic T lymphocyte function and augments anti-tumor activity, via up-regulation of its target gene


What is known?

It has recently been shown that blocking PD-1 with antibodies one could make tumors shrink. This work, relating to Cancer immunotherapy, has been chosen as Science’s breakthrough of the year.


Research Findings

This study suggests a natural product-based Human cancer therapy. N(1), N(11)-Diethylnorspermine, by increasing the expression of its target gene, it may suppress the expression of Glycogen synthase kinase 3-β (figure 1).

N(1), N(11)-Diethylnorspermine (DENSPM) க்கான பட முடிவு

Figure1. N(1), N(11)-Diethylnorspermine enhances cytolytic function of Cytotoxic T-lymphocytes, augments anti-tumor activity, and inhibits metastatic cancer progression via downregulation of Glycogen synthase kinase-3β and PD-1

Thereby, it may: (a) increase transcription factor T-bet expression; (b) inhibit co-inhibitory receptor PD-1 expression;  (c) increase CD8(+) cytotoxic T lymphocyte function; (d) augment anti-tumor activity; & (e) inhibit metastatic cancer progression.


Therapeutic opportunity

Thus, pharmacological formulations encompassing “N(1), N(11)-Diethylnorspermine or its analouges” may be used to inhibit the progression of tumors.


Details of the research findings:

Idea Proposed/Formulated (with experimental evidence) by: Dr L Boominathan Ph.D.

Terms & Conditions apply http://genomediscovery.org/registration/terms-and-conditions/

Amount: $100

Undisclosed information: How N(1), N(11)-Diethylnorspermine suppresses the expression of PD-1 and augments anti-tumor immunity

# Research cooperation

For purchase and payment details, you may reach us at admin@genomediscovery.org


References:

Citation: Boominathan, L., Natural product-derived PD-1 pathway blockade for Human cancer therapy:  N(1), N(11)-Diethylnorspermine (DENSPM), a spermine analog, decreases the expression of Glycogen synthase kinase-3β, increases transcription factor T-bet expression, decreases the abundance of co-inhibitory receptor PD-1 on the cell surface of Cytotoxic-T-cells, increases cytotoxic T lymphocyte function and augments anti-tumor activity, via up-regulation of its target gene, 8/December/2016, 11.33 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

Web: http://genomediscovery.org or http://newbioideas.com

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