Anticancer peptides

There is a series of cationic peptides that are capable of altering the electrical environment of the cell, disrupting it physiologically and causing the death of the cell as a result of affecting the pathways within the cells. The mechanisms of these peptides in altering the cell membrane are two fold. The first mechanism can may involve the peptide's interaction with the ion transport proteins of the cell. The second mechanism involves formation of ion channels per se (Kourie and Shorthouse, 2000). These peptides are available in nature and come from exotic creatures such as scorpions to bees and amphibians like frogs. I figure that targeting the electrical environment of cancer cells that result in their death might be one of the strategies in developing therapeutics against cancer.

Citations
Kourie, J.I. & Shorthouse, A.A. Properties of cytotoxic peptide-formed ion channels. Am J Cell Physio 2000 Jun; 278(6): C1063 - 87.

Of fullerenes and viruses

I chanced upon an article by RSC Publishing on the use of fullerenes conjugated to antibodies in anticancer therapies(RSC publishing, Ashcroft et al, 2006). Fullerenes are hollow buckyballs, which can be used to carry an assortment of anticancer drugs. The investigators made the fullerene more specific to target cancer cells by conjugating it to antibodies that recognize cancer. With anti-cancer viral therapy now in vogue and nanotechnology progressing, it would even be possible to produce a fullerene conjugated with viral coat proteins for specific targeting of cancer cells.

Citation
1) Fullerene promise in anti-cancer therapy accessible at http://www.rsc.org/Publishing/Journals/cb/Volume/2006/8/Fullerene_anticancer_therapy.asp

2) JM Ashcroft, DA Tsyboulski, KB Hartman, TY Zakharian, JW Marks, RB Weisman, MG Rosenblum and LJ Wilson, Chem. Commun., 2006

The cancer killing virus

In recent years, the use of virus to eradicate cancer have received a certain measure of success. The use of attenuated viruses with reduced virulence have been shown to be efficacious in certain form of cancers. The concept is simple. Allow the virus to reach the tumors, and the former will replicate within the latter, killing it. I have given this topic a long thought and I thought if it would be possible to infect the cancer cells, and then bring in the immune system to deal with the cancer cells, which were our normal cells gone awry, as though they were infected cells. It would be a combination of two hits on the cancer cells, with the viruses killing and lysing them, and the immune cells killing them too. Such recombinant viruses would have to express genes that are able to mobilize the immune system like the Monocyte Chemotactic Protein-1(MCP-1) and Interleukin-12 (IL-12), which can recruit and activate cellular components of our immune system like Natural Killer Cells, CD8 T cells, etc (Allavena et al, 1994). Under these inflammatory conditions, the Treg cells functions which downregulates immune response will be over-written. Thus, the first steps would be to sneak the virus into the tumour mass and infect the tumour cells, and subsequently, the tumour cells would be lysed by the viruses themselves and the chemokines and cytokines expressed by the tumours would recruit the immune system to kill the tumour mass. The immune system is seen something as a clean-up agent, which also wipes out any trace of the virus, which may persist in the body. However, in scenarios where the tumour cells express pro-apoptotic proteins like the FAS ligands in a mechanism known as the FAS counterattack, which induces apoptosis of immune cells, the efficacy of such a using such a recombinant virus might be reduced, and the reliance would be on the virus to replicate and kill off the tumour cells. However, in certain types of cancer like brain tumour and colorectal carcinoma, there is over-expression of the CD155 (Masson et al, 2001). CD155 can ligate the activating receptor of Natural Killer Cells and induce killing by the latter (Castriconi et al, 2004). Such a proposition makes the idea of recruiting our immune system to target the cancer cells' weakness(overexpressing CD 155) attractive.

Citations
1) Allavena P,Bianchi G,Zhou D,van Damme J,Jilek P,Sozzani S,Mantovani A. Induction of natural killer cell migration by monocyte chemotactic protein-1, -2 and -3.Eur J Immunol. 1994 Dec;24(12):3233-6.

2) Mavoungou E. Interactions between natural killer cells, cortisol and prolactin in malaria during pregnancy. Clin Med Res. 2006 Mar;4(1):33-41

3) Masson D, Jarry A, Baury B, Blanchardie P, Laboisse C, Lustenberger P, Denis MG. Overexpression of the CD155 in human colorectal carcinoma. Gut. 2001 Aug;49(2):236-40.

4) Castriconi R, Dondero A, Corrias MV, Lanino E, Pende D, Moretta L, Bottino C, Moretta A. Natural killer cell-mediated killing of freshly isolated neuroblastoma cells: critical role of DNAX accessory molecule-1-poliovirus receptor interaction. Cancer Res. 2004 Dec 15;64(24):9180-4.

Designing the potent cocktail

Multidrug resistance is a barrier to the treatment of cancer with chemotherapeutic strategies (Gottesman et al, 2002). P-glycoprotein transporters are responsible for the efflux of drugs from the cancer cells. A number of inhibitors have been designed for the multidrug resistance protein, for instance, the MDR-1 P-glycoprotein. These inhibitors will be added into the cocktail containing an arsenal anti-cancer drug to ensure a move effective treatment. However, side effects should be anticipated considering the fact that MDR drug pumps have a physiological role in our livers and kidneys.

Citations
1) Gottesman MM, Fojo T, Bates SE. Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Cancer. 2002 Jan;2(1):48-58.

Using hepatitis virus to fight liver cancer?

As my title suggests, it's one big irony considering the fact that hepatoma or hepatocellular carcinoma which involves transformation of hepatocytes is a consequence of viral hepatitis. Liver cancer has a high occurance amongst Asians. In recent days, anti-cancer viral therapy offers a great promise in the fight against cancer, which is why I was wondering if we could use an attenuated hepatitis virus to infect and kill the hepatoma cells. The Hepatitis B virus for instance targets hepatocytes. My suggestion was inspired by this experiment on a rat hepatoma cell-line, whereby scientists demonstrated the propagation of the human Heptitis B virus in vitro (Shih et al, 1989).

Citations

Shih CH, Li LS, Roychoudhury S, Ho MH. In vitro propagation of human hepatitis B virus in a rat hepatoma cell line. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6323-7.