advances-in-protein-chemistry

Future Perspective
Research into neoepitopes will provide important and novel means of diagnosis, prognosis and increasing treatment efficacy in
cancer. However, to fully take advantage of neoepitopes as highly valuable cancer biomarkers, it is very important to understand the
physiological mechanisms and signalling pathways that regulate their generation. Thus, the ultimate goal of new diagnostic tests should
be to use highly reliable non-invasive mechanism-based biomarkers. At present, receptors, cell adhesion molecules, growth factors
and enzymes, with their related protein substrates (e.g., MMPs and extracellular matrix components), are all hot research areas in the
development of cancer drugs and diagnostic assays [123].
In the past year, further evidence establishing the usefulness of β interferons and glatiramer in the treatment of relapsing-remitting
multiple sclerosis has been advanced. Interferon-β-1b was also shown to be efficacious in secondary progressive multiple sclerosis.
There are more than 20 MMPs identified that share several common features: signal peptides, prodomain, and prodomain, and catalytic
domain, with at least eight of these proteins clustered on chromosome 11 (MMPs -1, -3, -7, -8, -10, -12, -13, and -20), probably due
to a gene duplication event [124]. Johnson, PR et al., reported in 2001, that although the healthy adult lung is not a major source of
MMPs, parenchymal cells such as airway epithelium, fibroblast, and smooth muscle have the capacity to express active MMPs following
stimulation by a variety of agents such as infectious pathogens, environmental toxins, growth factors, and cytokines [125]. Lopez-Boado
et al. 2000 reported a 25-fold induction of MMP-7 in the lung epithelial cells following infection with Escherichia coli and Pseudomonas
aeruginosa, which could explain the up regulation of this enzyme in the airway of cystic fibrosis patients who are commonly infected
with these bacteria. It also has been shown that proinflammatory cytokines such as interleukin 1 beta (IL-1β) and tumor necrosis factor
alpha (TNF-α), upregulate the expression of MMP-9 in human airway epithelial cells following a 1-day treatment [126]. Additionally,
inflammatory cells invading the lung during the course of COPD are also a major source of different MMPs. It has been shown that the
neutrophils and macrophages, the predominant inflammatory cells in the lungs of COPD patients, have the capacity to release MMPs -2,
-3, -7, -9, and -12 [127].
Future of Cell Utilization for Disc Disease
Despite the growing number of research data on cell-based experimental therapy for IVD disease, it is clear that we do not know
much about native disc cells and their microenvironment. This lack of information is a major obstacle in building a strategy for the
treatment of IVD disease. Investigating the specific differentiation status of native IVD cells and their homeostasis will surely provide
more ideas and clues for efficient therapeutic approaches. Although cell-based therapy for IVD disease is still in its infancy, the stage of
testing a variety of cells for injection should be toned. To progress to the next step, we should be investigating what exactly IVD cells are,
and how they control their homeostasis, along with various studies optimising parameters, such as cell dosage and culture period and the
severity of IVD degeneration in the recipient [128].
Moreover, there is the need for attention to the stage and type of cancer that is likely to be evaluated in clinical versus preclinical
studies. For example, the selection of advanced pancreatic and lung cancers for clinical trials was based on considerations such as expected
survival time and patient availability, both of which affect the time and financial resources required to achieve statistically significant
results. Patent issues, competition, and impatience contributed to the decision to proceed at an unprecedented pace in an inappropriate
setting, and these factors will undoubtedly continue to influence drug development decisions in the future.
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