Modifying Bacteria to Treat Osteosarcoma

Researchers at the University of Nottingham from the School of Clinical Sciences’ Division of Pre-Clinical Oncology have recently done research on modifying harmless bacteria to create anti-cancer molecules. The specific bacterium being modified is Salmonella typhimurium, a harmless bacteria species. The team is led by Dr. Teresa Coughlan who is interested in modifying the bacteria in order to induce the production of molecules which kill cancer cells in osteosarcoma, a primary bone cancer. So far the team has been testing a clinically safe form of Salmonella typhimurium which localizes the tumor tissue rather than healthy tissue. About the specificity of the treatment Dr. Coughlan commented, “Developing a treatment that effectively targets cancer cells, but doesn’t damage healthy cells is the Holy Grail for bone cancer treatment.”

Currently, the main problem with treating bone cancer is finding a better way to only target the tissue affected by the tumor growth and not damage healthy tissue. Also, many anti-cancer drugs are given via intravenous injection which utilizes the vasculature system to transport the medication but tumors in bone have a low blood supply. By making the Salmonella typhimurium bacterium a transporter for caner killing molecules, Dr. Coughlan’s mission is to make bone cancer treatment more effective and specific. The molecules that are being investigated are called RNA interference molecules which would be produced in the bacterium and then released into the malignant cells of the tumor tissue in order to destroy the levels of cancer-causing molecules there.

I thought that this article was interesting because it involved so many topics of discussion that we have covered over the semester in class. One of the biggest issues that we have discussed is developing specific drugs that will have minimal side effects. In relation to the nanobot project, we have also talked a lot about noninvasive treatments and trying to align treatments with the body’s normal healthy functioning. All of these are important in this study of using a modified bacteria species to treat osteosarcoma with molecular medicine. One of the most impressive things about this treatment is its dynamic nature. Because the team is utilizing a preexisting and functioning organism to transport medication, they know that the “machinery” for it will be functioning. I think that these types of treatments will be utilized more and more frequently in the future as new organism are realized to be practical for homing in on certain diseases while carrying or producing medicine for the disease.

Article Source: http://www.medicalnewstoday.com/articles/204337.php
Alexander J. Quante '13 -- VTPP 434

Preventing the Spread of Cancer Cells

Researchers at Weill Cornell Medical College claim to have found the potential for a new class of anti-cancer agents through macroketone. The researchers published their findings in the online edition of the journal Nature. They have found that these new anti-cancer agents can stop the migration of metastatic tumor cells and therefore the spread of cancer.

The specific study involved implanting cancer cells into populations of mice and then treating them with small molecules called marcoketone. They found that the treated mice with cancer lived to a full life span in contrast with the control group which all died from metastasis. Even in mice that had the marcoketone introduced a week after the implantation of cancer still had an 80% block of metastasis. The researches are confident that this study is indicative of a new field of cancer treatment that is developing to specifically stop cancer metastasis. Dr. Haung, leading the research team at Weill Cornell, says, "More than 90 percent of cancer patients die because their cancer has spread, so we desperately need a way to stop this metastasis." Macroketone was developed from migrastatin, a natural substance that was isolated from Streptomyces bacteria by Japanese researchers. The researchers had noted that migrastatin had a weak inhibitory effect on the migration of tumor cells. Dr. Huang and his team took this substance and made synthetic versions that are a "thousand-fold more potent" than the migrastatin original.

The mechanism of macroketone is that it targets an actin cytoskelatal protein known as fascin which is needed for cell movement. Fascin bundles actin filaments together in order to make a kind of "foot" that can be used by a cancer cell to leave a primary tumor. The macroketone latches onto fascin and prevents actin fibers from adhering to one another which prevents this cell movement altogether. It is important to note that this treatment did not stop cancer cells from growing or forming tumors but it did prevent the spread of the cancer. The research team hopes that macroketone can be used in conjunction with another drug that would act on tumor cell growth. Dr. Huang also said about the minimal side effects that, "fascin is overexpressed in metastatic tumor cells but is only expressed at a very low level in normal epithelial cells, so a treatment that attacks fascin will have comparatively little effect on normal cells -- unlike traditional chemotherapy which attacks all dividing cells."

I found this article to be interesting because of the disease that was being discussed: cancer. Because cancer is such a deadly and widespread disease, there is a large amount of interest in investing time and money into the research of this disease. This leads to new discoveries being made everyday about the nature of cancer and the strides made in how to treat this disease. I also enjoyed the article because it dealt with taking a new perspective on cancer treatment. Instead of trying to treat tumorous tissue or individual tumors, the research team is attempting to control the cancer by not letting it spread through the body. Any new approaches to treating cancer are a step in the right direction to learn more about this disease.

Article Source: http://www.medicalnewstoday.com/articles/185482.php
Alexander J. Quante '13 -- VTPP 434

An Underlying Viral Cause to Prostate Cancer?

An unfortunate draw-back to being a man is the seemingly unavoidable risk of developing prostate cancer. Statistically, one in six men in the U.S. will be diagnosed with having prostate cancer in their lifetime; one in thirty-four of those men will die because of the cancer. Though the cause of prostate cancer has baffled researchers, a new study may have finally discovered the answer to this elusive problem.

Many theories and factors have been contributed to increasing the risk of prostate cancer, such as: age, race, and diet, but new research argues that prostate cancer may be linked to a virus. Researcher’s noticed the gammaretrovirus called Xenotropic Murine Leukemia Virus (XMRV) present within nearly one-fourth of cancerous prostate cells, and merely six percent of control cells. The findings suggest a possible correlation between the presence of XMRV and prostate cancer. Furthermore, a co-author of the study, Dr. Ila Singh, presented her conclusion that the presence of the virus denotes a more aggressive prostate cancer.

This finding is not the first time a virus has been attributed to cancer however. It has long been accepted that some cancers have a link to certain viruses, including: cervical cancer, lymphoma and sarcomas. In fact, Dr. Joseph DeRisi, a professor at UCSF and investigator at the Howard Hughes Medical Institute, states that 15 percent of cancers are actually known to be linked to viruses. In an entirely independent analysis a few years prior to Singh’s report, DeRisi also, noted the presence of XMRV in prostate cancer cells; however, a lack of adequate samples and a benign control group prevented a definitive relation.

Gammaretroviruses, such as XMRV, have been known to cause cancer in animals like rodents, cats and monkeys, but had previously been overlooked because they have never been found in humans until recently. Singh explains that retroviruses sometimes integrate onto the chromosomes of a host, and can cause a tumor by landing on a cellular gene; causing the gene to become overactive. Singh’s research team also managed to conclude that XMRV is not linked to a genetic mutation, a prevalent theory, meaning all men are potential carriers.

The study included a larger experiment, testing 233 cancer cell samples and 101 control samples, and Singh’s team did confirm that XMRV was indeed present. Singh’s next step is to determine whether the discovered correlation of XMRV and prostate cancer is in actuality the cause of the cancer, and she admits that it’s “going to take a long time and a lot of work to resolve”.

At the moment, the virus XMRV is the only viral link with the possibility of being attributed to prostate cancer. Unfortunately, researchers are still unsure of the all the systems at work in XMRV and how it is transmitted in the first place. DeRisi points out that what is of importance at the moment is discovering “whether XMRV is something all people are exposed to”.

Due to the prevalence of this particular cancer, the findings of Singh’s team may herald the first step in preventing a cancer that infects one-third of the world’s male population. Ultimately, if the underlying cause of prostate cancer is a virus, the possibility of a simple vaccination, similar to that being used to fight off Human Papillomavirus (HPV), could be employed world-wide; a phase Singh “hopes” her team can make a reality.

http://www.scientificamerican.com/article.cfm?id=retrovirus-linked-prostate-cancer
http://www.webmd.com/prostate-cancer/guide/prostate-cancer-risk-factors

Joshua Mott
VTPP 434-501

Bier mir!

Eat your vegetables, wash your hands, get your rest, and...have a beer? That’s right, next time you sit down to chomp on a juicy char grilled hamburger or flame kissed fillet, don’t hesitate to top it off with an ice cold beer, it might just do your body good. A recent study conducted in mice reveals that beer reduces the damage to DNA prompted by carcinogens found in overcooked meats.

Now before you go on a drinking binge, remember two important things. First, moderation is key. Second, this study conducted at Okayama University left out a certain component of the beer—its alcohol. Alcohol can be carcinogenic in its own right, so the researches only administered nonalcoholic beer to the mice.

Some mice were given the beer in place of water while others were administered the beer in solid form. A few days into their new diets, the mice were given two heterocylic amines (MeIQx and Trp-P-2), otherwise known as HCA’s, which are carcinogens found in cooked meat. Less than a week later, Dr Sakae Arimoto-Kobayashi analyzed specific cells in key organs for their adducts, or “HCA-induced DNA changes.” These adducts are thought to be the beginnings of cancer. Depending on the HCA administered, the kidneys, lungs, and/or liver were indeed affected. Amazingly, however, the mice that ingested the beer in one form or another had 40-75% fewer adducts than those who had no beer. While this relationship has not been confirmed for human subjects, I still find this cancer preventive connection quite interesting in that beer (again, in moderation) may not be all that bad. Though I am not a huge fan of O’Doul’s, after reading this article I now find some justification in having a beer or two in hopes that the good may in fact help balance the bad and the ugly.

Blake Cannon
http://www.sciencenews.org/view/generic/id/5937/title/Food_for_Thought__Beers_Well_Done_Benefit

Body Fat is Linked to Six Types of Cancer

We've all been told, "too much of anything is bad for you." The same is true of body fat. This Los Angeles Times article documents the work of the American Institute for Cancer Research's findings that relate body fat to cancer. It is known that excess body fat affects the levels of hormones and cell growth factors. Additionally, excess body fat is characterized by a low-grade chronic inflammatory state where the fat is localized, thus promoting or encouraging the growth of cancer. The report, found at www.dietandcancerreport.org, provides evidence connecting the growth of excess body fat to cancers of the esophagus, pancreas, kidneys and endometrium, colon and rectum, breasts of post-menopausal women.

Various recommendations are made as to how improving dietary, physical, and behavioral aspects of one's life will reduce body fat. Interestingly for steak-eaters, "Once an individual reaches the 18-ounce weekly limit for red meat, every additional 1.7 ounces consumed a day increases cancer risk by 15%." Therefore, too much of anything is bad for you.

http://www.latimes.com/news/nationworld/nation/la-na-cancer31oct31,0,4739640.story?coll=la-home-center

Whey Protein May Protect Against Prostate Cancer

You, or someone you know, uses whey as a dietary supplement. Many associate the protein as a means of gaining muscle mass for pre- or post-workout meals. However, the cheese byproduct has other advantages than purely body-building.

Scientists of Ohio State University treated male human prostate cells with whey protein in vitro. The cells, in response, increased cellular production of the antioxidant glutathione by as much as 64 percent. Glutathione is one of several antioxidants known to control the production of cancer-causing free radicals. Whey contains the amino acid cysteine, a key element in the synthesis of glutathione.

http://www.sciencedaily.com/releases/2003/05/030529081202.htm