Cancer 101-HB-19

I'm going to start with this paper.
But if you haven't read the intro yet, and you don't know much about cancer, you probably should start here.

Nucleolin is a potential target for tumor treatment for a number of reasons. Chief among these is the fact that nucleolin plays a role in angiogenesis, and as previously stated, without angiogenesis or metastasis, tumors cannot exceed a very small size. The researchers here used an antagonist to cell surface nucleolin (HB-19 and anti-nucleolin monoclonal antibody (mAb) which, while not resulting in disruption of normal cell metabolism and behavior, resulted in marked decreases in tumor proliferation. Another observation was that a marked decrease in cells at S phase was observed. This is consistent with the expected decrease in replication of cells via prevention of DNA replication.

Now for angiogenesis. The researchers then looked at VEGF stimulated HUVECs ("vascular endothelial growth factor" and "human umbilical vein endothelial cells" respectively) . When VEGF or PTN (pleiotrophin) were used, HB-19 and anti-nucleolin mAb had very similar inhibition of vascular formation. When FGF-2 (basic fibroblastic growth factor) was used, HB-19 had a much higher efficacy than anti-nucleolin mAb at decreasing angiogenesis.

They then had some fun torturing poor little athymic nude mice. They injected human breast carcinoma cells (that proliferate when untreated into palpable tumors in two weeks) into them. Following this, they began treatment with tamoxifen in some mice and HB-19 in others. Autopsy revealed no side apparent side effects compared to control mice injected with phosphate buffer solution (PBS) alone. The HB-19 treated mice also exhibited no side effects such as diarrhea, infection, weakness, lethargy, blood cell counts, or body weight. Mice treated with HB-19 also exhitibted some elimination of measurable tumors. HB-19 was also more efficient at treating tumors than tamoxifen in higher dose levels! Now, HB-19 was not as effective as 5-FU, however 5-FU has significant side effects on lymphocyte counts.

So, what does this mean? Well, firstly, HB-19 may make a very good auxiliary treatment for tumors. It may allow chemotherapy to be in much lower doses and far less frequently. This is one possible route for tumor treatment presented by this specific research. The other papers I'll be talking about will further explore ways to control and treat angiogenesis and thus, tumors.

The final installment can be found here.

Cancer 101

We'll start out with a few definitions:
Integrin-cell surface proteins which interact with the extracellular matrix
Angiogenesis-the branching and growth of new blood vessels by growth of new branches.
CXC chemokine-small proteins (CXCL4 has 70 residues) which play a role in chemotaxis
Specific proteins to know:

αvβ3-vitronectin receptor

α5β1-fibronectin receptor; also plays a role in angiogenesis

CXCL4-an αvβ3 antagonist found in platelets and plays a role in neutralizing heparin like molecules thereby enhancing coagulation

Now for some basics on cancer.

As tumors grow, they require more and more nutrients to feed the mass of cells. To accomplish this, they rely upon angiogenic factors to trigger growth of new blood vessels bringing oxygen and nutrients. Metastasis is one way tumors spread. This involves the migration of a cancerous cell into the blood stream and moving to another location and invading the surrounding tissue further downstream by use of integrin proteins. By stopping cancer from producing blood vessels and spreading, we can isolate tumors to very small masses in isolated locations making them far easier to treat with very specific radiation levels in very specific locations.

But first, we must prevent metastasis and angiogenesis. I'll cover that next time.

Part 2
Part 3