The Grand Finale!

Aside from studying for the final tomorrow the course has come to an end.  Today in class the remaining six students presented their audiovisual presentations.  There was a wide variety of topics:  sunscreen and cancer, red meat and cancer, stem cells in cancer, Helicobacter Pylori, occupational risks of firefighters and Kaposi’s Sarcoma.

To begin with, Masoud presented a rather amusing presentation of sunscreens and skin cancer.  Masoud used a number of visual affects that gained the attention of everyone.  The main points in Masoud’s presentation were:

• The difference between sunblock and sunscreen.  Sunblock literally reflects the sun’s rays by using active ingredients such as zinc oxide and titanium dioxide.  Sunscreen allows absorption of rays, however the sun’s rays dissipate before they can cause damage to underlying layers.
• The higher the SPF (Sun Protection Factor)  in sunscreen leads to a larger number of chemicals that the body is being exposed to. 
• There are three types of skin cancers: Basal cell carcinomas, Squamous cell carcinoma and malignant melanoma
• Skin cancer causes free radicals in the skin in three steps: initiation, propagation, and termination.
• The Wnt pathway is the major pathway affected in skin cancer.  Wnt binds to frizzled which activates disheveled.  Disheveled then activates teh GSK-3 complex that is bound to axin, which inhibits the degradation of B catenin.  The B catenin is then able to enter the nucleus of the cell and proliferation occurs.
• I have inserted a you tube video.  Masoud had this in his presentation, however time did not allow for us to view.  U.S Surgeon General Richard Carmona Talks About Skin Cancer

The next presentation of the day was give by me, and it was about the link that is seen from consumption of red meat and the incidence of cancers.  The main points of my presentation were:

• Nitroso compounds are formed in the body through the process of nitrosation.  Nitrosation occurs in the prescence of amides and amines (from meat protein) and the reduction of nitrates to nitrites.
• The pH of the human gastrointestinal tract is optimal for the growth of nitrate reducing bacteria.
• Heme is found in red meat.  People who consumed large amounts of Heme had higher levels of nitroso compounds in their fecal matter than individuals who took iron supplements.
• Heterocyclic amines (HCA’s) and Polycyclic aromatic hydrocarbons (PAHs) are formed during the cooking process of meats.  HCA’s induce mutagens through adduct induction of base pairs.  The adduction leads to misreplication events.  PAHs appear to be mutagenic due to the expression of cytochrome P4501A1 (CYP1A1), which metabolizes promutagenic PAHs.
• Keeping food as moist as possible can decrease the numberd of cooking mutagens that an individual will consume.
• Red meat has been linked to colorectal cancer, prostate cancer, pancreatic cancer, and breast cancer.

Tatianna presented the importance of stem cell research and possible cancer treatments.  Main points from Tatianna’s presentation were:

• Stem cells are self-renewing cells taht can give rise to other cell types.
• Stem cells can be obtained from adults and embryonically.  In adults, stem cells can be found in the skin, bone marrow, brain, liver, skeletal muscle and blood vessels.  Stem cells can be harvested embryonically through the cord blood, placenta and directly from a fetus.
• Certain defects in stem cells can lead to tumorogenesis.
• Numerous diseases have shown promise in being treatable through stem cell therapy, these include: Acute Lymphocytic Leukemia, Acute Myeloid Leukemia, Aplastic Anemia, Hodgkin’s disease and renal cell carcinoma.  Stem Cells Cure Leukemia
• Bone marrow transplants can occur in two ways: Autologous and alogeneic.  Autologus transplants are taken from the patients own body and then exposed to high doses of radiation before being reintroduced back into the patient.  Alogeneic transplants come from donors in which the bone marrow is collected through the blood or directly from the inner cavity of the bones.
• The future of stem cell research could lead to repairing damage to vital organs, growth of new organs and spinal repair.

Johanna presented the effects of the bacteria Helicobacter Pylori and its link to stomach cancer.  The main points from Johanna’s presentation were:

• H. Pylori is a spiral shaped bacterium that live in the lining of the stomach and duodenum.  H. Pylori has adapted to the harsh environment of the stomach by living in the lining of the stomach.  Also, H.Pylori release urease which hydrolysis urea to strong bases which neutralize the acidity of the stomach.
• H. Pylori is the most common bacterial infection, and is classified as a Class I Carcinogen, which means that it is carcinogenic to humans.
• H. Pylori can be contracted through oral contact such as kissing.
• H. Pylori can lead to gastritis, duodenal ulcers and gastric ulcers.  Eventually Gastric cancer can form if the H. Pylori is not cured.
• Ultimately, the immune response to H. Pylori that leads to cancer.  Immune cells cannot reach the bacterium since it is within the stomach lining, however the immune systems continues to try to attack the bacteria.  The immune system releases superoxide radicals which lead to the deterioration of the stomach lining.  The stomach lining is damaged to such a point that it is not protected from the acid and the stomach and duodenum can develop ulcers.
• The H. Pylori bacteria is detected in the body through blood tests, breath tests that detect the levels of CO2, stool tests for antigens and enoscopic biopsies.
• H. Pylori is highly treatable with what is known as triple therapy.  A proton pump inhibitor is used to reduce acid production and two antibiotics are taken.

Sarah works as a firefighter and did her presentation on the cancer risks that firefighter’s face.  Here are the main points from her presentation:

• Firefighters are exposed to many carcinogens cuch as asbestos, wood, plastics, household cleaners, chemicals, textiles and other hazardous materials.
• Firefighters can be exposed to such hazards through inhalation, absorption, injection and ingestion.  The absorption process is sped up in firefighters as the skin is moist and the conditions are hot.  injection and ingestion are less common paths to exposure but they do occur.
• Lung cancer is caused by diesel exhaust, which the firefighter’s are exposed to both at the fire station and on scene.  Lung cancers most commonly form as a result of a  mutation in the EGFR pathway.
• Skin cancer is caused by soot that is encountered.  Soot is present at all fire scenes and is produced from burnt coal, wood, oil, paper, plastics and other household items.  The pathway by which basal cell carcinomas for is the sonic hedgehog pathway. 
• Mesothelioma is caused by exposure to asbestos which can be inhaled by firefighters.  The cancer caused by asbestos is due to the physical properties, not its chemical makeup.  The fibers from asbetos are integrated into the pleura.
• Acute Myeloid Leukemia is caused from the exposure to Benzene which causes DNA breaks and mutations and leads to uncontrollable proliferation.   

The final presentation of the day was given by Samira about HIV, HHV-8 and Kaposi’s Syndrome.  The summary of Samira’s presentation is as follows:

• HIV is Human Immunodeficiency virus.
• HIV is a retrovirus which has two species: HIV-1 and HIV-2.  74% of the world’s cases of HIV occur in Africa.
• HIV is transmitted sexually, through blood, and through other bodily fluids.
• HIV infection has four stages: incubation, acute infection, latency and AIDS
• The treatments of HIV include:  HAART (protein inhibitors) and Azydothymidine (inhibits reverse transcriptase activity).
• Kaposi’s Sarcoma is linked to HHV-8 virus.
• Kaposi’s Sarcoma is a tumor that is caused by the incorporation of HHV-8 into B cells.  The tumors tend tobe vascular, sometimes they can be found in the lungs, liver and intestinal tract.

That is all that I have for the overview of our final day of presentations.  Everybody did an amazing job, I really learned a lot of new information.  Good luck tomorrow on the final, I wish you all the best of luck!

Canine Cancer Cure

I was watching the News this morning and saw a news story about a newly developed canine cancer cure. Apparently this treatment called Palladia was developed by Pfizer. In clinal trials at University of Ohio Veterinary branch palladia was successful in 60% of cases with mast tumor cells where the tumors either dissapeared, shrunk, or stopped growing . This cure Palladia is expected to be on the market in 2010. This news story caught me off guard I didn’t know cancer was also a issue for dogs and their owners. Wow!!! for more info visit this website:http://www.mlive.com/business/west-michigan/index.ssf/2009/06/pfizers_canine_cancer_drug_a_f.html

Day One of Presentations

I would also like to begin by saying what a great job everyone else who presented today did. If your like me presentations are often the most dreaded part of the semester! Hopefully I can refresh some highlights of the presentations given today as well as giving some new or different perspectives on the topics.

Andrew and NSAIDs as chemoprophylaxis

• NSAIDs are Non-Steroidal Anti-inflammatory Drugs
• The most prominent members of this group of drugs are aspirin, ibuprofen, and naproxen
• NSAIDs act as non-selective inhibitors of the enzyme cyclooxygenase, inhibiting both the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) isoenzymes
• Prostaglandins establish the inflammatory response. NSAIDs interfere with prostaglandin production by inhibiting cyclooxygenase
• Celebrex is a non-steroidal anti-inflammatory drug (NSAID) that is used to relieve the pain, tenderness, inflammation (swelling), stiffness caused by arthritis, menstrual cramps, and colonic polyps
• Celebrex is a COX-2 inhibitor that works specifically on an enzyme called COX-2. COX-2 inhibitors are newly developed drugs for inflammation that selectively block the COX-2 enzyme. Blocking this enzyme impedes the production of the chemical messengers (prostaglandins) that cause the pain and swelling of arthritis inflammation. Cox-2 inhibitors are a new class of non-steroidal anti-inflammatory drugs (NSAIDs). Because they selectively block the COX-2 enzyme and not the COX-1 enzyme, these drugs are uniquely different from traditional NSAIDs.
• Pros and Cons

Colby and Target Cancer Therapies

• Cancer is a diverse cellular disease
• Precision vs. Accuracy
• Classic Treatments: Surgery, Radiation Therapy and Chemotherapy
• Standard chemotherapy: drugs that attack rapidly dividing cells, lacks precision and cell signaling research with Tamoxifen
• Targeted therapies enter the scene as the “magic bullet”
• Targeted therapies targets the differences between normal and cancerous cells
• New Generations of treatment which are designed at the molecular level and target cell signaling interactions
• The characteristics of what makes a good target cell
• Subclass; Small molecule which blocks specific enzymes and GFRs needed for tumor maintenance and Apoptosis-inducing which causes cell to undergo apoptosis by interfering with specific proteins.
• Gleevec which is a Tyrosine Kinase inhibitor that works through competitive inhibition

Sara J and Cancer Vaccines

I was particularly interested in this topic due to the recent controversies of the HPV vaccine being administered to young girls.  I did a little bit more research and found this site which gives a little more information on the HPV vaccine. http://en.wikipedia.org/wiki/HPV_vaccine

• A cancer vaccine is a vaccine that either prevents infection with cancer-causing viruses, treats existing cancers, or prevents the development of cancers in certain high-risk individuals
• Two major classes; Prophylactic vaccines which are preventative vaccines and Therapeutic vaccines
• Adjuvants and their relationship to cancer vaccines
• Pros of cancer vaccines
• Challenges to creating an effective vaccine
• Collaborating treatment options
• Future of cancer vaccines

Araba and Testicular Cancer

• Testicular cancer is tumor found in one or both of the testes
• Testicular cancer is highly treatable (especially when detected early) and usually occurs in younger populations
• Male reproductive anatomy http://www.patient.co.uk/showdoc/21692440/
• Causes of testicular cancer include germ-cell tumors and stroma tumors
• Risk factors which include un-descended testes, abnormal testicle development, family history, age and race
• Symptoms of testicular cancer
• Testing and diagnosis
• Treatments: Surgery, radical inguinal orchiectomy, re-tropretitoneal lymh node dissection, radiation therapy and chemotherapy
• Prevention and self-examination steps

Me and Environmental Estrogens and Their Ties to Cancer

• Three major classes of estrogen occurring in the body
• What estrogen naturally does in the body
• Estrogen and its link to breast cancer
• Estrogen implicated in breast cancer risk because: its role in stimulating breast cell division, its role in breast growth and development and its effect on other hormones that stimulate breast cell division
• Risk of breast cancer is related to females lifetime exposure to estrogen
• Environmental estrogens are defined as any group of synthetic substances found in the environment that, when absorbed into a person’s system, function in a similar way to estrogen
• Two types of environmental estrogens; Xenoestrogens (chemicals- found in plastic, pesticides and personal care products) and Phytoestrogens (plant foods- sunflower seeds, flax seed, caffeine, and other foods)
• Xenoestrogens have been linked to breast and ovarian cancer because they can bind to the natural estrogen receptor and cause cell proliferation
• Ways to Protect Yourself from environmental estrogens

Matt and Hepatitis B Virus (HBV) , Cirrhosis and Heptocellular Carcinoma (HCC)

• Definition of HBV and some statistics about it http://en.wikipedia.org/wiki/Hepatitis_B
• Cirrohosis is the consequence of HBV
• Hepatocellular Carcinoma (HCC) is a primary cancer of the liver
• Risk factor of HCC
• Molecular mechanism inducing hepatocarcinogenesis
• Liver cell proliferation is high during chronic hepatitis
• Telomere shortening hypothesis
• Impaired hepatocyte proliferation
• Four main changes that lead to HCC

http://www.hepatitisbannual.org/article.asp?issn=0972-9747;year=2004;volume=1;issue=1;spage=140;epage=152;aulast=Mohandas

Wow, that is a lot of content covered in one day.  I hope this outline and the links I provided help you in sumerizing the topics we covered today! Good luck for those who have to present tomorrow!

The beginning of the end…

I would like to start off by saying what an awesome job all of our presenters did! Part of me was really glad that the presentations were saved for the last few days of class, because I don’t know about you guys, but I know that I’m in overdrive trying to cram all the knowledge that has been offered over the past 2+ weeks into some sort of sensical order before the final friday. So, what a nice refresher. As far as presentations go we had the following people talking about the following topics and sorry guys if i miss anything.
First up we had Andrew who informed us about NSAIDs as chemoprophylaxis and how most are based around COX2, and we see this in some drugs like celebrex, but there are pro and cons that must be considered before it’s had.
Second up was Colby who talked about the “magic bullet” to cancer treatment which was really based upon targeted therapies, the treatment of cancer, and some of the significance behind the research. The thing that i found most astounding was the cost of the cancer drugs. Part of me can see that the money needs to back into the pharmaceutical companies to fund more research, but the other part of me feels as though if someone needs these drugs and can’t pay though insurance or other means then why not just give it to them.
Third, we had Sara, and the discussion of cancer vaccines. I thought that this topic was really cool, but its a shame that more cancers can’t be prevented with just a shot. Of course a big one with that is HPV and how it can lead to cervical or penile cancer.
Break Time
Fourth on the list was Araba who enlightened us about testicular cancer and how there are two main types, and how important it is for men to perform self-examinations of the testicular region and consult a doc if things seem a bit strange in the nether regions. The thing that made me chuckle a bit about this topic was the idea behind a fake testicle, but if it a guy feels better about the situation then more power to him.
Fifth Trisha did her presentation on environmental estrogens and how they play a role in cancer. She let us know about the different types of estrogen and the type that is mimicked by environmental estrogens. In that there are two main categories of environmental estrogens 1) xenoestrogens, the chemical kind and 2) phytoestrogens, the plant kind. Also hitting on the reduction of estrogen in the body can reduce the risk of breast cancer.
The sixth and final presentation for the day was Matt. Matt presented on hepatitis B and how it can lead to liver cancer, and how there are an astronomical number of people that die from this or some other problem with the liver.
This concludes the summary of our day, and I wish you all luck in studying for the final, as well as the presentations that are coming up tomorrow.

I Know that I Don’t Know

As an undergraduate biologist, I always naively believed that I had a near complete understanding for cancer.  My knowledge of cell biology, biochemistry, and genetics gave me confidence in my explanation of the disease as:

-A mutation in one’s own cells, provocated by radiation i.e. UV light or anything unhealthy known as a “carcinogen*”, that causes the cell to copy itself without limits, creating a useless mass of cells known as a tumor that eventually metastizes into the bloodstream and wreaks havoc on the body’s organs systems.

*Off topic, why do we call all cancer causing mutagens “carcinogens?” The root words of that term should mean “carcinoma genesis”. So a “sarcogen” should be the term used for mutagens that cause sarcomas.

I’ve lived all my years in fear of cancer as a time-bomb waiting to inflict death upon loved ones older than me.  I thought treatment for cancer always involved a harsh regimen of hospitalizations with surgery, chemotherapy and radiation, which would weaken and disable that person for long periods of time within the treatment.  My conventional knowledge of the disease lead me to believe that those harsh treatments were the only possibility and advancements were logically impossible.  I thought that “carpet bomb” treatment is the only way to eradicate the non-targetable disease of ones own cells known as cancer.

Tumor Viruses – Our Final Lecture

Today in class we covered our last set of lecture material on tumor viruses.  There seems to be a variety of viruses that cause cancer in animals, but not in humans.  There are only a few viruses that cause cancer in humans.   One of these viruses is HPV16 , which causes cervical cancer in women and penile cancer in men.  Furthermore, SV40 is believed to cause mesothelioma in individuals.  It was originally thought to be caused by contaminated polio vaccines but this was proved to be false.  Instead, like other DNA viruses, SV40 has the potential to cause tumors; however, it generally results in a latent infection.

Tumor virus genomes, such as SV40, will migrate and become integrated into the genome of the host cell that is going to be affected.   The presence of SV40 can be detected using molecular techniques.  If the viral DNA is covalently bonded to large genomic DNA, then the tumor virus genome has become integrated into the cellular host genome.

SV40

Slow Transformation

One of the key findings concerning viral genomes like SV40 is that they randomly integrate into a host cell genome.  In turn, this results in slow acting transformation of the host cell.  A viral genome has the chance of integrating next to a protooncogene such as myc.  This causes viral promoters to engage in overexpression of protooncogenes. This method, called insertional mutagenesis, is used to convert a protooncogene into a oncogene.  This is what is responsible for 80% of all Avian Leukosis Virus sarcomas found in chickens.  The ALV genome is integrated next to the myc gene.  This leads to its overexpression.   The chances that a virus will integrate next to a protooncogene are slim.

From studying slowly transforming viruses, researchers were able to construct a list that identified a number of genes involved in cancer.  These included oncogenes and tumor suppressor genes.  Important genes for slow transforming viruses include p53, erbB2, ras, and myc.

Acute or Rapid Transformation

Acutely, or rapidly transforming viruses are found to integrate into host cells.  In fact, the RSV tumor virus that is going to integrate into the host genome evolved from ALV.  It appears that rapidly transforming viruses have a oncogene with it when it integrates into the host cell genome.  The oncogene’s presence drives cellular transformation.  It seems that many of these types of viruses can be classified as retroviruses.  They use a mechanism to make DNA from an RNA genome.  Acutely transforming viruses integrate their newly synthesized DNA into the host cell chromosomes.

When a acutely transforming virus decides to infect a cell, it may integrate next to a protooncogene like ALV does.  ALV typically integrates its genome beside the src protooncogene.  When new viral genomes are made, protooncogenes may be incorporated into the viral RNA.  These protooncogenes may experience random mutations and be changed into oncogenes.  This results in RSV (Rous Sarcoma Virus), which obtains the src gene that will lead to sarcomas.

Acutely transforming viruses are special because they play a role in the discovery of many different oncogenes that are known to be important in human cancers.  Some examples of acutely transforming viruses that led to notable oncogenes include src, myc, ras, jun, sis, and erbB2.

HHV8, HIV, and Kaposi’s Sarcoma

There is a relationship between the human herpes virus 8 (HHV8) and Kaposi’s sarcoma.  HHV8 causes Kaposi’s sarcoma, which is a rare form of cancer of the endothelial cells.  The endothelial cells make up the vasculature of the sarcoma.  HIV relates to Kaposi’s sarcoma in that there is a much higher occurrence of Kaposi’s sarcoma in areas where HIV is endemic.

Kaposi’s Sarcoma 

How does the mechanism of HHV8 lead to Kaposi’s sarcoma?

The immune system can usually eliminate cells that are infected with HHV8; however, when the immune system is undergoing suppression, it is unable to eliminate cells infected with HHV8 and the virus takes hold.  HHV8 has several mechanisms to drive tumorgenesis and create sarcomas.  The involvement of KSHV-GPCR will drive signaling through multiple pathways.  The Ras pathway, the PI3 kinase pathway, as well as other pathways, are known to drive proliferation and force the expression of growth factors.  Furthermore, proliferation and the suppression of apoptosis are continually active due to GPCR, which uses an autocrine signaling loop to keep these processes going.

HPV and Cervical Cancer

It appears that a virus causes another form of cancer.  Cervical cancer may be caused by either HPV16 or HPV18.  These are high-risk viruses that tend to have a strong correlation with cervical cancer.  There are also risk factors that increase the chance of HPV causing cervical cancer.  These include smoking, the use of birth control for greater than 5 years, the number of lifetime sexual partners, age, and immunodeficiency.  Like Kaposi’s sarcoma, there is a higher incidence of cervical cancer in countries that are endemic for HIV. 

Other types of HPV, including HPV6 and HPV11, do not cause cervical cancer; rather, they lead to genital warts.  It appears that these forms of HPV are low risk viruses and they have no correlation to cervical cancer.   It has been found that two-thirds of people exposed to HPV6 or HPV11 will develop genital warts.

The Mechanism Behind HPV

It appears that there are two oncogenes responsible for HPV.  These are E6 and E7.  E6 stimulates the addition of ubiquitin chains to p53, which degrades p53.  This means that apoptosis is suppressed.  Tumorgenesis takes place and abnormal cell division cannot be controlled by cell death.  Furthermore, HPV also has a mechanism to drive cellular proliferation and tumor formation. 

E7 is a viral protein that will bind to another protein in the infected cell called Rb.  E7 operates by binding to Rb and causing displacement of transcription factors so that the cell will progress through the cell cycle, even if there are no appropriate cues from the environment to drive it.  After the cell goes through the cell cycle, the virus will drive cell division.  Cell division cannot be stopped since the virus is suppressing apoptosis.  Many tumor viruses are formed from interfering with Rb and p53.  Sometimes p53 will make up for the loss of function of Rb.  P53 will invoke apoptosis and the HPV virus is strong enough to overcome the compensation of the mechanism of p53.

After lecture we discussed in groups the literature paper concerning the functioning of p53 and the formation of tumors.  This group review helped students to formulate their answers to the discussion questions.  The day ended with Dr. Duncan briefly going over the exam requirements and letting us look at a list of 10 potential exam questions, 5 of which we can research the answers ahead of time.

To Test or Not to Test…

This appeared in my New Scientist RSS feed this morning:

http://www.newscientist.com/article/mg20227102.800

While I believe in genetic testing because it facilitates informed choice, I’m not sure how I would feel about mandatory testing. I think that this would rapidly be taken to task by liberty groups and end up in the European Court of Human Rights as being an infringement of Article 8 of the Convention of 1950 (Right to respect of private and family life).