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Title: Solving the puzzle about Bowhead whale longevity and its low risk to cancer

<a href="http://biolecture.org/images/3/35/Research_paper_Bowhead_Whale_Madina.pdf" title="Research paper Bowhead Whale Madina.pdf">Research_paper_Bowhead_Whale_Madina.pdf</a>&lrm;

<ph1>Abstract: </ph1>

Bowhead whale is the longest living organism and have enormous body size, body mass. According hypothesis, their cells have to proliferate plenty times, in the long run this organism should have high risk to cancer, but it is surprisingly vise versa.  There is should be regulation involved in Bowhead whale, which is contributes to repress cancer in their body.

Deep diving of the whale in bottom of ocean, induces hypoxia in the organism. Remarkably, in tumor same condition occurs, and in the human body they succeed to induce angiogenesis, in outcome formed vessels supply cancer cell, which will further grow and increase migratory and metastasis.  This paper suggest that Bowhead whale angiogenesis process that manage hypoxia condition in whale body may play important role in repressing cancer.  Moreover, paper includes current anti-angiogenesis drugs in clinical approaches, and tries to find solution to their side effects.

<ph1>Introduction:</ph1>

One of the longest – living animals of the earth is the Bowhead whale (Balaena mysticetus), which is estimated to live over 200 years. These animals can weigh from 75 to 100 tons, and live entirely in <a href="https://en.wikipedia.org/wiki/Arctic_Ocean" title="Arctic Ocean">Arctic</a> and sub-Arctic waters. [1]

<ph1> The problem: </ph1>

The most abundant baleen Minke whale is the closest relative to the Bowhead whale, which diverged from each other only 25-30 million years ago. [3] The catching thing here is that, even though they have around 96%  matched protein coding sequences, their characteristic features highly remarkable.

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It is highly accepted that during the tumor, cancer cells deprives from oxygen supply, due to active proliferation level of the cells. So, in tumor regions oxygen concentration level significantly lower than in healthy tissues. This condition called tumor hypoxia, and cancer cells alter metabolism in order to support their growth, replication.  Furthermore, due to hypoxia tumor cells change their behavior, like extracellular matrix remodeling and increased migratory and metastatic behavior. [5] The mechanism that cancer cells turn on during the hypoxia condition is that they release their target genes in angiogenesis, such a vascular endothelial growth factor (VEGF), as a result the new blood vessel formation will happen, which encourages above described tumor behavior.

There are required close look to the every single gene variants, since almost all protein coding genes almost same with a minke whale. In paper, introduced above, scientists tried to look to ever bowhead-specific amino acid replacement mechanisms in DNA repair, or cell-cycle proteins. However, I wish to investigate Bowhead specific amino acid changes in proteins responsible to angiogenesis process.

<ph1>The details:</ph1>

Cells undergo a variety of biological responses when placed in hypoxic conditions, including activation of signaling pathways that regulate proliferation, angiogenesis and death. Cancer cells have adapted these pathways, allowing tumors to survive and even grow under hypoxic conditions, and tumor hypoxia is associated with poor prognosis and resistance to radiation therapy. Many elements of the hypoxia-response pathway are therefore good candidates for therapeutic targeting (Harris, 2002).[8]

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<h4p> Gene Details</h4p>

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<h4p>Gene match (Cow)</h4p>

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According to outcome, 21 amino acid changes in VEGF co regulated chemokine 1 were observed, among them 12 amino acid had non-synonymous variation.  These modifications could lead to specific features to the angiogenesis. There are also more proteins that responsible to new vessel formation in organism. So further research indeed necessary.

<ph1>Related works:</ph1>

For the cancer therapy, anti-angiogenesis drugs commonly used in clinics, especially vascular endothelial growth factor (VEGF) inhibitor agents most popular among cancer treating drugs. To give an example, Bevacizumab (<a href="https://www.cancer.gov/Common/PopUps/popDefinition.aspx?id=CDR0000367431&version=Patient&language=English">Avastin</a>®) is an antibody that specifically recognizes and binds to VEGF, so making it unable to attach and activate the VEGF receptor.[11] In addition, it was one of the first angiogenesis inhibitors, and showed positive results in medication, like halting tumor growth, and also could prolong cancer patient’s life. There are other anti-angiogenesis drugs, like sorafenib and sunitinib, which cease angiogenesis in different way: bind to receptors on the surface of endothelial cells or to other proteins in the downstream signaling pathways, blocking their activities [12].

<ph1>References: </ph1>

[1]  <cite>Rugh, David J.; Shelden, Kim E. W. (2008). "Bowhead Whale". In Perrin, William F.;</cite> <cite><a href="https://en.wikipedia.org/wiki/Bernd_W%C3%BCrsig" title="Bernd Würsig">Würsig, Bernd</a></cite><cite>; Thewissen, J. G. M.</cite> <cite>Encyclopedia of Marine Mammals</cite> <cite>(Second ed.). Academic Press. p. 131.</cite> <a href="https://en.wikipedia.org/wiki/International_Standard_Book_Number" title="International Standard Book Number">ISBN</a> <a href="https://en.wikipedia.org/wiki/Special:BookSources/978-0-12-373553-9" title="Special:BookSources/978-0-12-373553-9">978-0-12-373553-9</a><cite>.</cite>

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<h2p>[7] <a href="http://www.jle.com/fr/recherche/recherche.phtml?dans=auteur&texte=Christiane+Brahimi-Horn">Christiane Brahimi-Horn</a>, <a href="http://www.jle.com/fr/recherche/recherche.phtml?dans=auteur&texte=Jacques+Pouyss%C3%A9gur+">Jacques Pouysségur</a> “The role of the hypoxia-inducible factor in tumor metabolism growth and invasion”. Published in 2006 on <a href="https://www.google.co.kr/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiy1Ljl4dTQAhVLTbwKHXasC0oQjhwIBQ&url=http%3A%2F%2Fwww.jle.com%2Ffr%2Frevues%2Fbdc%2Fe-docs%2Fthe_role_of_the_hypoxia_inducible_factor_in_tumor_metabolism_growth_and_invasion_269705%2Farticle.phtml%3Ftab%3Dimages&bvm=bv.139782543,d.dGc&psig=AFQjCNHOAtqOfUdlhbjU4ER9GFPRkQmsag&ust=1480742493553300" target="_blank">John Libbey Eurotext</a> websit <a href="http://www.jle.com/fr/revues/bdc/e-docs/the_role_of_the_hypoxia_inducible_factor_in_tumor_metabolism_growth_and_invasion_269705/article.phtml">http://www.jle.com/fr/revues/bdc/e-docs/the_role_of_the_hypoxia_inducible_factor_in_tumor_metabolism_growth_and_invasion_269705/article.phtml</a></h2p>

<h2p>[8] Harris AL, “Hypoxia: a key regulatory factor in tumor growth”, National Review in Cancer 2002 January; 2(1): p. 38-47.</h2p>

<h2p>[9] Sequence details CXCL17 bmy_22314 (Coding sequence)</h2p>

<h2p><a href="http://www.bowhead-whale.org/annotations/details/bmy_22314/">http://www.bowhead-whale.org/annotations/details/bmy_22314/</a></h2p>

<h2p>VEGF co-regulated chemokine 1 precursor (Human) <a href="https://www.ncbi.nlm.nih.gov/protein/NP_940879">https://www.ncbi.nlm.nih.gov/protein/NP_940879</a></h2p>

<h2p>Homo sapiens C-X-C motif chemokine ligand 17 (CXCL17) <a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_198477">https://www.ncbi.nlm.nih.gov/nuccore/NM_198477</a></h2p>

<h2p>[10] Blast results:  <a href="https://blast.ncbi.nlm.nih.gov/Blast.cgi">https://blast.ncbi.nlm.nih.gov/Blast.cgi</a></h2p>

<h2p>[11] Shih T, Lindley C. Bevacizumab: an angiogenesis inhibitor for the treatment of solid malignancies. Clinical Therapeutics 2006; 28(11):1779–1802. </h2p>

<h2p>[12] Gotink KJ, Verheul HM. Anti-angiogenic tyrosine kinase inhibitors: what is their mechanism of action? Angiogenesis 2010</h2p>

<h2p>[13] By Melissa Hogenboom “The animal that does not get cancer” on BBC website, posted 31 October 2015 <a href="http://www.bbc.com/earth/story/20151031-the-animal-that-doesnt-get-cancer">http://www.bbc.com/earth/story/20151031-the-animal-that-doesnt-get-cancer</a></h2p>

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