Pathways

The BCR signalling pathway is a pathway that plays a vital role in the development and all other functions of B-cells, which means it is vital for the immune response. The BCR, also known as the B-cell receptor, is usually found on the outer membrane of B-cells. B-cells grab antigens from immune synapses, through a number of processes including cell spreading and receptor transport. After these have been performed, endocytosis and antigen-presentation occur. B-cells manipulate the dynamic of BCR-antigen bonds. They group and spread the antigen, increasing the relation with BCR, which creates sensitivity. The two main functions of the BCR pathway is to signal transduction, and the second is to prepare the antigen for processing by the helper T cells. Any defects in this pathway may lead to the patient being immunodeficient, or having B-cell malignancy.

The BCR signalling pathway is a pathway that plays a vital role in the development and all other functions of B-cells, which means it is vital for the immune response. The BCR, also known as the B-cell receptor, is usually found on the outer membrane of B-cells. B-cells grab antigens from immune synapses, through a number of processes including cell spreading and receptor transport. After these have been performed, endocytosis and antigen-presentation occur. B-cells manipulate the dynamic of BCR-antigen bonds. They group and spread the antigen, increasing the relation with BCR, which creates sensitivity. The two main functions of the BCR pathway is to signal transduction, and the second is to prepare the antigen for processing by the helper T cells. Any defects in this pathway may lead to the patient being immunodeficient, or having B-cell malignancy.

The BCR signalling pathway is a pathway that plays a vital role in the development and all other functions of B-cells, which means it is vital for the immune response. The BCR, also known as the B-cell receptor, is usually found on the outer membrane of B-cells. B-cells grab antigens from immune synapses, through a number of processes including cell spreading and receptor transport. After these have been performed, endocytosis and antigen-presentation occur. B-cells manipulate the dynamic of BCR-antigen bonds. They group and spread the antigen, increasing the relation with BCR, which creates sensitivity. The two main functions of the BCR pathway is to signal transduction, and the second is to prepare the antigen for processing by the helper T cells. Any defects in this pathway may lead to the patient being immunodeficient, or having B-cell malignancy.

The BCR signalling pathway is a pathway that plays a vital role in the development and all other functions of B-cells, which means it is vital for the immune response. The BCR, also known as the B-cell receptor, is usually found on the outer membrane of B-cells. B-cells grab antigens from immune synapses, through a number of processes including cell spreading and receptor transport. After these have been performed, endocytosis and antigen-presentation occur. B-cells manipulate the dynamic of BCR-antigen bonds. They group and spread the antigen, increasing the relation with BCR, which creates sensitivity. The two main functions of the BCR pathway is to signal transduction, and the second is to prepare the antigen for processing by the helper T cells. Any defects in this pathway may lead to the patient being immunodeficient, or having B-cell malignancy.

The BCR-ABL fusion protein is a cytoplasm-targeted constitutively active tyrosine kinase that causes uninhibited cell proliferation via signalling cascades. This fusion protein is the result of a genetic abnormality known as the Philadelphia chromosome in which Abelson Murine Leukemia viral oncogene homolog 1 (ABL1) translocates within the Breakpoint Cluster Region (BCR) gene on chromosome 22. The action of BCR-ABL produces chronic myelogenous leukemia (CML), a cancer characterized by increased and unregulated growth of white blood cells in the bone marrow and the accumulation of these cells in the blood. Physiologically, ABL is a tyrosine kinase involved with cell growth that moves between the nucleus and the cytoplasm. Upon fusion with BCR, the oncoprotein is constitutively activated due to a preference for dimerization or tetramerization promoting subsequent autophosphorylation, and it is retained in the cytoplasm. BCR-ABL activates several oncogenic pathways which promote increased cell proliferation and survival including the MAPK/ERK Pathway, the JAK-STAT Pathway, and the PI3K/Akt pathway. BCR-ABL forms a complex with GRB2, GAB2, and SOS that activates Ras (converted from its inactive GDP-bound state to the active GTP-bound state). Ras signalling triggers the MAPK/ERK pathway which stimulates abnormal cell proliferation through regulation of transcription and translation. The BCR-ABL/GRB2/GAB2/SOS complex also activates STAT5 either through direct phosphorylation or indirectly through JAK2 kinase to promote survival. Additionally, JAK2 kinase activates the MYC transcription factor for growth-related genes. The PI3K/Akt pathway can be activated either via the BCR-ABL/GRB2/GAB2/SOS complex or the BCR-ABL/CRK/CRKL/CBL/PI3K complex. Akt functions in: (1) increasing cell proliferation by promoting the degradation of p27 (CDKN1B) through the upregulation of SKP2; (2) enhancing protein translation (and subsequently increasing cell proliferation) by activating mTOR kinase; (3) and preventing apoptosis to ensure survival by inhibiting both FOXO transcription factors and the protein Bcl2-associated agonist of cell death (BAD) as well as activating MDM2 which inhibits the tumour suppressor p53.

Beclomethasone dipropionate is a corticosteroid used in the treatment of asthma, bacterial sinusitis, dermatosis, and many other conditions. Inflammatory conditions involve the activation of cascades by inflammatory mediators. Beclomethasone dipropionate works by attenuating this inflammatory response. Cases of Candida albicans infection of the mouth and throat have been reported with inhaled beclomethasone dipropionate therapy because of its suppression of the immune system. Beclomethasone dipropionate is a prodrug that is rapidly metabolized to 17-monopropionate by hydrolysis by esterases CYP3A. It is this metabolite that mediates the anti-inflammatory actions. As 17-BMP is the active metabolite, it is a glucocorticoid, and its mechanism of action is that of the glucocorticoid response element (GRE) of influencing COX-2/prostaglandin G/H synthase 2 suppression and lipocortin/annexin induction. By binding to the glucocorticoid receptor, it influences transcription factors AP-1 and NF-kB to block the transcription of COX-2/prostaglandin G/H synthase 2 which reduces the amount of prostanoids being produced from arachidonic acid. Prostanoids such as PGI2 and thromboxane A2 influence the effects of inflammation through vasoconstriction/dilation, pain sensitivity, and platelet aggregation. 17-BMP also affects the promoter of annexin-1, an important inflammatory protein as it affects leukocytes and blocks phospholipase A2 which reduces the amount of arachidonic acid being cleaved from the phospholipid bilayer. Reducing the amount of arachidonic acid formed further decreases the concentrations of prostanoids mentioned calming inflammation. Beclomethasone dipropionate has many routes of administration such as inhalers, nasal sprays, topical lotion, and oral capsules.

Bedaquiline is a drug that is not metabolized by the human body as determined by current research and biotransformer analysis. Bedaquiline passes through the liver and is then excreted from the body mainly through the kidney.