Tuesday, June 12, 2012

Geographical Distribution as a Risk Factor

While my partner and I were researching HPV related cervical cancers and trying to see if there was a geographical factor that contributed positively or negatively, I came across an article about a study done in Jingan County, China that specifically focused on this question.

The study took a group of women from different terrains and by excluding the known factors that increase the risk of cervical cancer were able to monitor the geographical influence on cancer.

Cancer Causes Death...But It's Not What You Think

            Obviously cancer is deadly.  It is a disease that attacks the cells in our body and creates mutations that make its own cells immortal, but is dying from cancer the only worry that cancer patients should have?  Based on the article, Non-cancer mortality among people diagnosed with cancer, we see a trend in the deaths of cancer patients versus non-cancer patients, and notice that the higher death rate among people with cancer is not always necessarily due to cancer.  So why do cancer patients have a much higher chance of dying from a non-cancer related mortality?  What does this say about lifestyles, health related issues, and even psychological aspects of the disease?

Monday, June 11, 2012

Forks Over Knives Part 2: Examining the Validity of Scientific Studies

In the beginning, Dr. Islas gave us a short list of lifestyle changes that could be made to combat or slow the onset of cancer. Wear sunscreen. Exercise. Avoid smoking. Eat Healthy.  In a 2011 American documentary directed by Lee Fulkerson, this idea of eating healthy as a means to combat degenerative diseases and reverse the growth of cancerous cells is explored through promotion of a “Whole Foods Plant Based Diet” while simultaneously reviewing the works of American physician Caldwell Esselstyn and professor of nutritional biochemistry T. Colin Campbell, two of the most prominent advocates for the diet in America. (You may remember this from the blog post “Forks Over Knives: How a Whole Foods Plant Based Diet Can Cure You”).
In response to the documentary, I asked for the general thoughts and opinions of the class on the evidence presented and if you would consider the whole foods plant based diet. Well, since I did not note a significant rise in veganism on campus I would venture to guess that most of you still do not think of milk protein as a carcinogen and animal based proteins are still a staple in the majority of your diets, skeptical of the claims that a whole foods plant based diet can cure all ailments and prevent cancer. You are justified in your skepticism.

Saturday, June 9, 2012

Go Ahead, Eat Me...Oh but Wait...Don't Eat Me! said the Cancer Cell (Revised)

In a 2010 article from Stanford School of Medicine, research lead by Mark Chao and Ravindra Majet details interesting insight into the machinations of cancer cells. The researchers and their team discovered that many cancer cells actually carry the wellspring of their own ruination, this is in the form of a protein, calreticulin (CRT), an 'eat me' signal on the cell surface of cancer cells that signals circulating immune cells to engulf and digest them. So how come cancer cells are not destroyed efficiently by microphages? Now this is where it starts to get interesting, get this, cancer being the genius that it is also produces separate 'don't eat' me signals in the form of CD47 proteins on cancer cell surfaces creating a process that works to counteract the 'eat me' (CRT) signals.

Can an Anxious Heart lead to Cancer (revised).

Who knew an anxious heart could have a link to cancer?
Over the winter break I browsed through a book entitled, Healing Begins with the Sanctification of the Heart by Dr. Strydom, a Zimbabwean lady who got her training and qualification to be a medical doctor in South Africa. Dr. Strydom, in her insightful book discusses how anxiety and stress can be detrimental to one's health. According to her research, stages 2 & 3 of stress (contributors to prolonged stress) cause excessive production of stress hormones in the human body including ACTH- 'the fear hormone' and cortisol. Cortisol in excessive amounts kills T cells of the immune system, and when this happens T & B cells go out of balance and B cells become overactive and begin to produce excessive antibodies, this then means that the immune system no longer functions efficiently and that the individual in question becomes more susceptible to attack by bacteria and viruses. I would like to venture further and hypothesize that knowing what we previously learnt in lecture about some viruses causing cancer, I believe that anxiety can indirectly lead to cancer via the transformation of viruses and v-oncogenes which are not destroyed by the immune system. Furthermore, we know that one of the hallmarks of cancer involves evading immune system destruction (Hanahan, Weinberg), therefore, in this case, if the immune system is already down or functioning at a less than efficient level, cancer cells may just better thrive in such an environment because a weak immune system won't be able to efficiently ward off viruses and cancer cells.

Re-educating Tumor-Associated Macrophages

In an article published in 2008, Thorsten Hagemann and his fellow researchers identified a method to change tumor-associated macrophages (TAMs) into cytotoxic macrophages, which would then be able to target tumor cells as do normal MI macrophages.
Adoptive transfer of IKKβ-targeted TAMs inhibits tumor growth in vivo. Iluminescence imaging shows the amount of TAMs as a result of no treatment or treatment with dominant-negative inhibitor of IKKβ.

Oncogene Amnesia and Addiction

Is anyone else working on the papers about Oncogene Addiction and Oncogene Amnesia. I would like to initiate a 'discussion' online about the paper. Let me know if you are interested!

Targeting Tumor Associated Macrophages

Figure 6(A) Elimination of TAMs results in
a reduction in tumor angiogenesis (1)

In our cancer project "Host Immune System Enhancing Tumor Growth" as you may recall we went over an interesting immunotherapy experiment in which targeted tumor associated macrophages (TAMS) were destroyed by targeting legumain to identify target molecules. Here I will take a more in-depth analysis of this experiment to better understand it's pros and cons.

Friday, June 8, 2012

Curry Spice Can Kill Cancer Cells?


In an article by the BBC, researchers discovered the chemical curcumin (found in the curry spice, turmeric) could help kill oesophageal cancer (cancer of the esophagus) cells. The rate of oesophageal cancer has gone up by more than a half since the 1970s as a result of rising rates of obesity, alcohol intake and reflux disease, according to the researchers at the Cancer Research facility in the UK, and curcumin might be a viable treatment. A team at the Cork Cancer Research Centre in the UK found that curcumin induced "apoptosis-independent death" in oesophageal cancer cells.

The Mutations Cancer Avoids

As a final blog, I came across something interesting on the internet. Usually we equate cancer proliferation with a mutation that results in a loss of function and the cell begins to replicate uncontrollably. However, a study published online today showed that while nuclear DNA of cancer cells has many mutations, the same is not the case for mitochodrial DNA (here). In fact, the scientists found that colorectal cancer cells has three times fewer new mutations than normal colon cells. The type of mutations found in normal colon cells were typical mutations in response to oxidative damage: C:G to T:A transitions. When you consider that cancer cells rely more on anaerobic glycolysis for energy as opposed to oxidative phosphorylation, the contrast becomes clearer. The scientists speculate that with fewer mutations, the cancer cell mitochondria function better, thus the cancer cells have a better metabolism and can live longer, if not forever.

The Ethics of Genomics

Quick Blog: I wanted to take a departure from the complicated science and assess the progress of genomics as it relates to cancer diagnostics/therapy. If you read the countless blogs from the entire quarter, it is evident that scientists are able to study cancer on a molecular level and essentially map cancer risk based on genome sequencing. As much as this technology will pioneer breakthrough treatments, it also begs the question, "how far is too far?" In an article published online Wednesday, it was announced that the fetal genome can be determined from a maternal blood sample and a paternal saliva sample. In the theme of genomics and the possibility it provides, here is some food for thought:

  • Could genomics potentially dissuade couples from reproducing?
    • If genetic screening becomes universally accessible, many couples may choose to learn of the risks that they may be subjecting their offspring to. 
  • Should there be legal statutes against reproducing if a couple knows that their offspring has a heightened risk of cancer or any other disease?
  • What impact will genetic screening have on abortion legislation?
  • Is genetic sequencing bestowing an extra element of worry or a gift of knowledge?

Lynch Syndrome: When the Molecular Cleaning Ladies Stop Working.

Lynch Syndrome; 

When the Molecular Cleaning Ladies Stop Working.

A few week ago my mom went to the SGNA (Society of Gastrointestinal Nurses and Associates) conference in Arizona. While there she attended lecture on hereditary colon cancer by Dr. Larry J. Geier, the director of the Genetic Risk Evaluation and Testing (GREAT) program. She told me about what a great lecture it was and I was able to get ahold of his lecture slides and contacted him about his sources. As his lecture focused on Lynch Syndrome, I'll be using, Dr. Wendy Kohlmann's review on LynchSyndrome, his primary source on the subject from his lecture.

Lynch syndrome is an autosomal dominant genetic syndrome that effects approximately 1 in every 350 people. There are numerous mutations that cause Lynch syndrome and interestingly they can appear in any one of 5 recognized genes; MLH1, MSH2, MSH6, PMS2, and EPCAM. The first four genes are involved in the mismatch repair process. This is to say that they repair nucleotides that have been incorrectly paired during DNA replication. The last one, EPCAM, is special and I'll get to it soon. The MLH1, MSH2 and PMS2 protein product all bind together to for the Mismatch Repair Complex that actively binds to mismatched nucleotide bases and matches them correctly. The MSH6 protein product has more of a support function in the overall process. A detrimental mutation need only exist in one of the genes in order to significantly reduce the function of the overall complex. When this happens, the Mismatch Repair Complex is incapable of adequately repairing the mismatches between DNA replications. As a result, in the following DNA replication when the DNA helix spits and replicates, one of the daughter cells will have mutation where the unfixed mismatch appeared. Over time and many DNA replications, mutations accumulate. Each mutation occurs randomly, but follows the “bull's eye theory” (ie. If I throw enough darts, eventually I'll hit a bull's eye).

Figure 1. Microsatellite instability testing is used to identify tumors caused by defective mismatch repair by comparing the number of nucleotide repeats in a panel ofmicrosatellite markers in normal tissue with the number from tumor tissue from the same individual. Microsatellite stability (MSS) is present if the same number of repeats is present in each marker in both the tumor and the normal tissue. Microsatellite instability (MSI) is present if the number of repeats in the tumor and the normal tissue differs

As I wrote about early, the WNT pathway in the cell plays a major role in tumorigenesis in adenocarcinoma of the colon. If a mutation occurs within any protein in the Axin-TCF-APC complex protein genes (as is often the case in adenocarcinoma of the colon resulting from Lynch syndrome), then B-catenin goes under-regulated within the cell, complexes with TCF and promotes the oncogene c-MYC, which leads to the synthesis of Cyclin A and Cyclin E, the activation of CDK2 and CDK4, and the suppression of P27. As we learned in class the actication of the Cyclins A and E and CDK's 2 and 4 promote the movement of the cell into and through S-phase of the cell cycle, essentially causing the cell to proliferate. Since this mutation will remain in the cell in the subsequent daughter cells, there will be a continuous over-expression of c-myc leading to continuous over proliferation of the cell as seen in Familial Adenomatous Polyposis (FAP). Essentially, simply by providing a stream of unfixed de novo mutations, Lynch Syndrome can create a novel incidence of Familial Adenomatous Polyposis (FAP) within an epithelial mucous cell of the colon. Naturally, the mutation could also take place in the promoter or early exons of the c-MYC gene that would cause it to be expressed more readily. As long as the mutation occurs somewhere within the WNT pathway and leads to the over-expression of the c-myc gene, the end result will be polyposis.

Next comes EPCAM, which I personally find amusing. EPCAM isn't a Mismatch Repair protein. The reason it's involved with the functioning of Mismatch Repair Genes is because it sits just upstream of one on the chromosome. I find Dr. MatthiasKloor's study on EPCAM expression in Lynch Syndrome better explainsthe proposed mechanism. As it happens, deletions in the EPCAM gene in the 3' exon a and coincidentally need the promoters of the MSH2 Mismatch Repair Gene, can cause a problems with the functionality of the promoter, such that MSH2 is simply read through without expression. The molecular mechanism isn't very clear, but I believe that the deletion either causes a histone binding site or stop/start codon top blend in with the neighbor's nearby genetic code. Essentially, a deletion in it's upstream neighbor's gene effectively silences MSH2. This opens a lot of doors for possible gene interactions in adenocarcinoma of the colon and more. As only one fifth of the adenocarcinoma of the colon attributed to genetic risk factors have genetic risk factors that we can identify, we can now see that germline mutations in some genes can be caused by nearby genes in the genome that aren't normally mechanistically associated with the genes that are being silenced more mutated. I believe the saying, “there goes the neighborhood” rather effectively summarizes EPCAM's effect on MSH2 and by extension the Mismatch Repair pathway and resulting cancers.

A question I'm sure everyone has is, why Lynch only causes adenocarcinoma of the colon when its mutations are random? It doesn't. Lynch causes increased risk of a number of differenct cancers. Adenocarcinoma of the colon simply happens to be the premiere example of cancers it causes as it raises the probability of formation of 5% to ~80% and it happens to be my subject matter.

The question I have is; how was an oncogene as powerful as c-CYM be moderated by medice. The gene is essentially an on/off switch for cancer. It cascades into such a wide variety of proto-oncogenes and oncogenes that over-activation of it practically guarantees you'll develop cancer. It's like the Lynch pin (pun intended) and pressure point of cell proliferation. All molecular roads in adenocarcinom lead to and through the c-MYC gene. If we could learn to properly moderate it expression, then we could prevent the grand majority of colon cancer.

  1. Kohlmann, Wendy; Gruber, MS; Gruber, Stephen B (2011). Lynch Syndrome. 2004 Feb 5 [Updated 2011 Aug 11]. In: Pagon RA, Bird TD, Dolan CR, et al., editors. GeneReviews™ [Internet]. Seattle (WA): University of Washington, Seattle; 1993-.
  2. Kloor, Matthias; Voigt, Anita Y; et. All (2011). Analysis of EPCAM Protein Expression in Diagnostics of Lynch Syndrome. Journal of Clinical Oncology, 29(2):223-7.

Give Up the Bacon (Or Eat Less)

To change things up, this blog post will focus more on the social aspects of cancer rather than the molecular basis of the disease. Specifically, I want to discuss the consumption of red meat and the growing body of evidence linking it to cancer. 

So at the beginning of class, Dr. Islas tried to convince us to make lifestyle changes that would reduce our risk of developing cancer. He suggested that we always wear long sleeve shirts and pants (especially during the summer!) and especially for us to avoid eating meats that were BBQed.

I am guessing that many of you, even with ten weeks of cancer biology under your belts, are not going to make such drastic lifestyle changes. Odds are we will continue to wear our swimsuits and we will probably continue to eat meat.

All of this made me wonder about our threshold for behavioral trade-offs. In other words, how high must the risk for cancer be before we make dramatic changes in the way we live? For many of us, we are willing to tan outside, but are unwilling to even venture into a tanning booth. But what about changes in our diet? One major difference between tanning and diet is that how we eat has generally been indoctrinated in us from a very young age. As a result, changing eating habits can be much more difficult.  For those of us that have always been told that eating fatty foods such as McDonald's or KFC is unhealthy, avoiding fast food isn't hard.  But this is normally the case with red meat. Based on my personal experience and other anecdotal evidence, a majority of individuals believe that meat is a healthy part of diet. There is the belief that red meat is the best source of protein.

Although I know it is unlikely,  my hope is to persuade some of you to reduce your consumption of red meat. It may not be easy, but research is showing over and over again that carcinogenic effects of red meat.

Detecting Cancer by MSP

MSP (methylation-specific PCR) detects hyper and hypo methylation of genes through a bisulfite modification. As a review CpG island promoters that are methylated are silenced. Cancerous cells are usually observed to have hypermethylation of genes that result in silenced tumor suppressor genes. Usually, the hypermethylation is due to an excess expression of DNA methyltranserase which are responsible for methylating the promoters by attaching a methyl group to a cytosine base. Rather than using traditional restriction enzymes to cleave distinguish methylated from unmethylated DNA for PCR, MSP (Methylation specific PCR) modifies DNA with sodium bisulfate which converts all unmethylated cytosines to uracil (8). The sodium bisulfate does not affect methylated cytosines, allowing clear distinct comparisons of methylated vs unmethylated DNA.

Epigentic Therapy


DNA methylation as a biomarker to detect and assess tumor growth is only one part of the cancer equation. New studies show the active role of epigenetic changes in development of a treatment of cancer. Traditionally, clinic treatments involve radiation, surgery or drug poisoning. The introduction of a class of drugs that target some proteins in the cancer pathway seems promising. These drugs are referred as "epi-drugs" in a study done by Juergens and colleages (11). Epi-drugs target the DNA methylation machinery such as inhibiting DNA methyltransferases (DNMTi). By interfering with the methylation, some cancer tumor suppressor genes will not be silenced, thus a epigenetic therapy. The patients whose specific genes were unmethylated responded well to traditional therapies such as radiation after the epigenetic therapy. The demethylation of those genes made the cancerous cells more susceptible to chemotherapy.

Eating Healthy; One of the Best Treatments for Genetic Predispositions to Adenocarcinomas

I came across a study rather similar to one of the examples Dr. Chernikova shared with us in her lecture; the one concerning the effects of a healthy diet on breast cancer occurrence in mice. There are, however, a two key difference between the study Dr. Cherikova bright up and this study, done by Dr. Volker Mai. First, instead of correlating dietary habits in mice to breast cancer, Mai looked into adenocarcinomas of the gastrointestinal track. Second, all of the mice within this study were bred to be carriers of APCMIN, which give them the mouse equivalent of Familial Adenomatous Polyposis (FAP). I wrote early on FAP, but the short story is that, in humans, its genetic disorder that results in hundreds to thousands of polyps in the colon and intestines due to a mutation in the APC gene that leads to over-expression of the WNT pathway.

Mai tested mice within four treatment conditions. Aside from the control group which was fed normal pellets, one group was given a diet with a calorie restriction 40% below the control, one was given a high fat diet, and the last a diet high in olive oil and supplemented with freeze-dried fruits and vegetable extracts with a total calorie count similar to that of the high fat diet. After nine weeks on the diets, necropsies were performed on all the mice. The results are nicely summarized below in Figure 1.

Figure 1. Mean (± SE) polyp numbers in ApcMin mice after 9 weeks of dietary treatment. Total polyps (▪), total polyps > 2 mm (□), colon polyps (▨). Control (n = 30); Calorie-restricted (CR) [n= 28; P versus control (total polyps) <0.0001]; Supplemented (OFV) [n = 30; P versus control (total polyps) = 0.04]; and High fat (HF) = high corn oil [n = 14; P versus control (total polyps) = 0.5].

As you can see above, there are significant differences in the numbers of total polyps (black bars) per mouse in each treatment group. The calorie restricted (CR) diet and the supplemented diet (OFV) obviously both resulted in notably lower average polyp counts than the control and high fat (HF) diets. This trend hold when the count is restricted only to polyps greater than 2mm in length, though the relative range has decreased notably. Once restricted to solely colon polyps, the results become too close to be considered significant.

Ignoring the colon-specific results, diet appears to be a firm factor in the formation of adenomas. The 40% restricted diet resulted in 57% fewer polyps on average relative to the control (P < 0.05). It's important to note that this reduction was not great enough to result in malnutrition. This large of a contrast is rather self explanatory. If these results hold true in follow up studies and carry over to humans, then calorie restriction definitely a viable means of deterring polyp formation in carriers of Familial Adenomatous Polyposis (FAP) and very possibly the numerous other genetic disorders characterized by increased risk of adenocarcinoma.

The high fat (HF) diet, while having accrued the highest average number of polyps, was not significantly larger than the control (P = 0.5). The supplemented diet (OVF), however, resulted in 33% fewer polyps on average (P = 0.04), which marks it as another viable dietary option in deterring polyp formation. With the supplimented diet, however, the best comparison that can be made is to the high fat diet as it as the overall calorieintake, food mass and % kilocalories from fat are close in both these treatments, the difference in polyp count can be attributed to the nutritional difference between the two diets. No r-value is available for this comparison, but there does seem to be a significant difference between the two diets. This suggests that in lieu of calorie restriction, people partaking of a high fat diet can simply change the contents of their diet without having to restrict calories and deter polyp formation to a significant degree.

The fact that these mice carry the equivalent of Familial Adenomatous Polyposis in humans makes the result especially promising. Given the sheer quantity in which polyps form in the colon and intestines of these patients, a 33-57% decrease in polyps can easily equate to thousands of prevented polyps over a lifetime. Such a deterrent could easily grant these patients years of additional time before the disease either overwhelms them or they're forced to undergo a colectomy (removal of the colon) as is commonly the case and results in numerous digestion complications. Furthermore, calorie-restricted and nutritionally-supplemented diets are relatively cheap means of preventing polyp formation.

Despite the strength of the overall results, personally, I initially found these results rather disappointing. As my topic revolves around andenocarcinoma of the colon, it was frustrating to find such clear distinctive results from the total polyp count while the results from only the colon came out to be statistically insignificant. The problem is how low the average number of colon polyps per mouse is. With each treatment group containing only 14-15 mice and the average colon polyp count in each group landing well below 0.5 polyps per mouse, significant results would be nigh impossible to achieve.

In addition to a larger test group, the study would have needed to extend beyond nine weeks in order to allow colon polyps more time to form and grow. Unfortunately, this probably isn't a viable option. Given how aggressively polyps formed within the small intestine during these nine weeks, any significant increase in the length of the experiment would probably prove sufficiently long enough for the polyps in the small intestine to kill off a significant number of mice in the control and high fat diet treatment groups. Possibly, by using a different animal model, significant results on the colon alone could be produced. However, despite the statistically insignificance of the colon-only data, the functionality of the formation of adenocarcinoma in the small intestines is highly comparable to that of the large intestines, so the the overall results are at least indicative of a possible trend in the colon as well.

We've got to chill out - hakuna mata!

We have all heard that stressing about things doesn't really get us anywhere. When we freak out about taking tests or completing projects it doesn't really matter how much we work or study because in the end we end up affecting our performance by psyching ourselves out. I'm sure that at some point in our college experience we all can relate to a moment in which we had such a high level of stress that we can no longer compute a single train of thought. Ring a bell? I'm sure it does, especially when finals are approaching fast and furiously. Interestingly, some schools are aware of the negative effect that stress has on academic performance and overall mental integrity of students. Because of this, they are implementing an innovative technique to help students release stress through the presence of puppies. You read correctly, puppies are now the answer to our stress! Currently, schools around the nation are using the "Dogs on Campus" approach, where students are able to interact with puppies, that are part of a social training program to become companion dogs, as a way to break away from  their stressful studies. For instance, in Harvard Medical School and Yale Law school, therapy dogs are now held in libraries and are capable of being rented by students, especially during finals. The reasoning behind this unique stress relief technique applied by these schools is that they have seen a positive correlation between the mental state of students and the time they spend interacting with the dogs. Research on this matter suggests that the interaction with pets decreases the levels of cortisol, a primary stress hormone, and increases hormones such as endorphins, which have been associated with the increase of happiness to levels in which students can perform normally as their stress levels return to optimal levels.

So how does stress have such a potent effect in our body, and how can we neutralize it when no canine love is available?

Thursday, June 7, 2012

CD95/CD95L Application to Tissue Grafts

      My cancer presentation delved into discovering the role of CD95/CD95L in tumor counterattack and the validity of such an escape mechanism. While researching this mechanism I came across an older paper that suggested future studies in this area may be able to apply CD95/CD95L to increasing the stressfulness of tissue grafts. So I got onto google and searched to see if this mechanism had been applied to tissue grafts yet, and sure enough there is an ongoing effort to utilize cancer's trickery to aid the medical community. Here are the results of my research, but first, some background information on CD95/CD95L, allogeneic immune response and the current therapies used to treat side effects of tissue grafts.

       CD95/CD95L is a ligand and receptor set typically used by T-cells to induce apoptosis in pathogens or non-self cells. Here is a simplified version of how this system works.

Education in conjunction with consistent Screening and Treatment= Reduced Incidences of HPV-related Cervical Cancer in Developing Nations?

My partner Kayla Ehring and I are studying viruses and how they lead to cancer. Particularly, our focus has been on the HPV virus and its link to cervical cancer, especially in developing countries.

Case studies:
I recently stumbled upon a 2010 study entitled, Examining attitudes about HPV and cervical cancer risk among female clinic attendees in Johannesburg, South Africa. It got me thinking about possible solutions to solve this sad development in developing nations, especially those in Africa, a place very close to my heart.
 In the 2010 study  it is revealed that developing countries account for up to 85% of the approximate 500,000 cases per year of cervical cancer globally. Approximately 250,000 of these deaths occur in Sub Saharan Africa, South Asia and Latin America. One suggested cause for the high rates of cervical cancer in developing countries may be attributed to the lack of efficient methods of screening for and treating HPV and cervical cancer. 
According to the WHO, cervical cancer is treatable, but many women in developing countries do not have access to effective screening programs, thus explaining the high incidences of cancer in developing countries. Furthermore, according to studies published by the NIH in 2001, incidences of cervical cancer are so high in developing countries primarily because of the lack of effective screening programs aimed at detecting and then treating precancerous conditions. In  the study, an estimated 5% of females in developing countries had been screened for cervical dysplasia in 5 sequential years, where as in developed nations at least 40%-50% of the women had been screened for cervical dysplasia. 
Furthermore, while developing nations do offer pap smear services, in many cases, these tests are only available to a small number of women, via private health care. In short lack of technology, lack of follow up diagnostics and treatments are largely to blame for the high incidences and prevalence of cervical cancer in developing nations. The graph below graphically represents this point very well.

Figure 2

Furthermore, in the  2010 study in South Africa, 86 women aged 18-44 with at least one offspring, were enlisted to take part in a survey which aimed to understand the attitudes and knowledge women in South Africa had about HPV, cervical cancer and the HPV vaccine. The results reflected that a significant portion of the participants were not familiar with HPV, the vaccine and cervical cancer, they were however concerned about the risk to both them and their offspring of acquiring HPV and cervical cancer. The study also reflected the fact that many of these women faced barriers towards receiving screening for cervical cancer but were willing to get their offspring vaccinated. This study reflects the need for education in developing nations such as South Africa about HPV, how it is contracted and how it can lead to cancer. Such invaluable knowledge could offer a major break through in terms of reducing incidences of cervical cancer in the developing nations.
Below is a sample of some of the results from the survey and study:
Womens' knowledge about HPV:

Table 1:Sample interview and results on HPV
Participants’ response
C1. Have you ever heard of HPV infection
29% (n = 86) yes
C2. HPV is a sexually transmitted disease/infection
79% answered true
C3. There is no cure for HPV but it can be controlled
33% answered true
C4. Having HPV puts one at risk for cervical cancer
67% answered true
C5. HPV is an infection that only affects women
17% answered false
C6. HPV is spread through sexual contact
71% answered true
C7. Condoms offer some protection from HPV
75% answered true

Werner Syndrome: Aging in Fast Forward

Let’s face it: Nobody likes to age.  The thought of growing old makes most cringe and scramble to find a miracle cure to halt this process.  Skin care companies make fortunes selling wrinkle creams to make women look ten years younger, hair dyes are sold right and left to get rid of those gray hairs, and Botox has become almost a common procedure in America.  The only thing worse than getting old and wrinkly?  Doing it at an increased rate.  Werner Syndrome is a form of adult progeria, characterized by premature aging, and it is no surprise that telomeres have everything to do with it.

Wednesday, June 6, 2012

The Link Between Socioeconomic Status and Cancer

In class we’ve discussed many aspects of cancer. Some of these had to do with the most prevalent types of cancer in the United States, the survival rates, treatments, cancer risks, and many other related topics. There is one possible related risk factor which we did not discuss: socioeconomic status of the patient. In an article titled, Impact of Socioeconomic Status on cancer incidence and stage at diagnosis, scientists explore the relationship between socioeconomic status and cancer incidence. Combining data from the Surveillance, Epidemiology, and End Results (SEER) Program at the National Cancer Institute, a population-based cancer registry, and the US representative National Longitudinal Mortality Study (NLMS), which provides self-reported demographic and socioeconomic data, researchers were able to examine the connection between the two.

Tuesday, June 5, 2012

I'm not crazy: Thioridazine really does target cancer stem cells

Research has shown that the drug, Thioridazine, an antipsychotic drug normally used to treat Schizophrenia, may also be used as a targeted treatment for cancer.  While Thioridazine killed a precursor to leukemia cells, it did not harm the normal cells – the ultimate goal with all cancer treatment.  By targeting only the leukemia cells, thioridazine has the potential to permanently eradicate them, such that a secondary tumor never forms.

Monday, June 4, 2012

Metformin and Radiation Therapy

           The pancreatic cancer presentation last week discussed the drug Metformin, which is one of the most widely used drugs in type 2 diabetes treatment.  The presenter mentioned it interestingly has anti-growth effects.  I decided to investigate this drug further in the context of cancer and found this study.  These researchers tested the effects of Metformin on MCF-7 human breast cancer cells and FSaII mouse fibrosarcoma cells.  The results suggest that Metformin can cause a significant amount of clonogenic cancer cell death.  Even more stunning is that the drug was preferentially cytotoxic to cancer stem cells (CSCs) relative to non-cancer stem cells.  Also, these researchers investigated the effect of Metformin on cancer cells being treated with ionizing radiation and found that it increased the radiosensitivity of the cells.  In effect, the Metformin “helped” the radiation kill the cancer cells.  This idea is very similar to my comments at the end of my presentation last Friday in which I mentioned the possibility that drugs taken in combination with traditional therapies could increase the desired effect against cancer cells while decreasing the negative effects on normal cells.  This study provides some compelling initial evidence in support of this theory. 

Saturday, June 2, 2012

Can Jaws Help Save Cancer Patients?

I have always been obsessed with sharks and while researching for a blog entry I remembered reading something years ago about sharks being linked cancer. It was the belief that shark cartilage or liver oil supplements were in fact the cure for cancer.

Kill Sonic Kill Cancer?

             Pancreatic cancer is a death sentence. It is quick to metastasize, hard to detect, and resistant to treatment. Following resection, radiation and chemotherapy are used to eradicate the remaining bits of the tumor that are left behind. These have not proven all that effective at leaving the patients cancer free. Pancreatic cancer is quite hard to access using chemotherapy due to its poor perfusion and desmoplastic (growth of fibrous or connective tissue) stroma. To add to confusion, the therapeutic window, the balance between toxicity and efficacy, of many chemotherapies is quite small. (The researchers refer to this as the “therapeutic index”). Additionally, chemotherapies have very short half-lives and often do not reach their desired target because of this. Researchers speculate that by increasing vasculature and preventing the accumlation of connective tissues in the stroma, chemotherapies would more easily reach and apoptose their targets.

Friday, June 1, 2012

Inside the Industry of Cancer: Pricey or Priceless?

My Photo of 1500 Owens St. San Francisco, CA 
Three months ago I had the unsuccessful, yet fortunate, opportunity to interview for an internship at C--- Corporation in San Francisco. Approaching the executive park I had no idea what to expect; perhaps white walls, white ceilings, lab coats- you know, like Willy Wonka, but super high tech, so maybe more like Area 51. As I approached the building with profusely perspiring palms and pits, I realized I might have misconstrued the rising biotech industry of the Bay. Yet, I was still shocked by the fourteen-story glass monolith before me, just a stone's throw from the Bay.

UV Radiation and Skin Cancer

Every time you expose your skin to sunlight, UV rays penetrate your skin. The more exposure, the higher the risk for the UV light to cause mutations. Have you ever wondered why this happens? How does UV light cause mutations? There are a lot of factors that contribute to the risk for skin cancer. In my previous blog I talked about indoor tanning, which is a voluntary exposure to UV rays but in this blog I want to talk about involuntary exposure. I also discuss how location/migration affect your risk.

A Genetic Disease That Virtually Guarantees You'll get Colon Cancer

FAP: A Disease that Virtually Guarentees you get cancer.

Imagine a disorder that virtually guaranteed you'd develop colon cancer not only within your lifetime, but early in it. One such disorder is Familial Adenomatous Polyposis (FAP), also known as Gardner's Syndrome. In the review article, Familial adenomatous polyposis, by Elizabeth Half, Dani Bercovich, and Paul Rozen, the specifics of this remarkable and deadly disorder are laid out.

Tuesday, May 29, 2012

Lung Cancer and Cigarette Smoke

     I read a paper studying the correlation between rates of cigarette smoking and lung cancer incidence in the United States.  It seems pretty common knowledge today that cigarettes contribute to cancer, but this paper offered some insights into the issue I had previously not thought of.  The paper, found here, analyzes these two things based on different birth cohorts and provides figures showing lung cancer incidence from the early 20th century, lung cancer based on different cohorts and smoking rates in teenagers. However, the figures offer an overly specific analysis with too narrow of a date ranges to show the change in lung cancer incidence in relation to change in smoking rates nationally. In order to get a better visual of how the rates mimic each other I decided to create a figure presenting smoking rates and lung cancer incidence for both males and females in the United States from 1965-2005. The data for smoking came from the CDC and the data for lung cancer came from the American Lung Association.

Here are the figures I used before I combined the lines.

First the lung cancer figure from the American Lung Association:

Transcription Factor KLF11, Diabetes, and Pancreatic Cancer

Image Above: Six insulin molecules in a hexamer (6).
KLF11 also known as, TIEG2, is a pancreas transcription factor that has started to gain attention due to its discovered role of being a negative regulator of exocrine cellular growth both found in vitro and in vivo. This is a very interesting case because for the first time KLF11 has been characterized as a glucose regulated transcription factor specific to the insulin gene. In addition, type II diabetes has been linked too two rare variants of the KLF11 gene and has been found to impair transcriptional activity. KLF11 works by altering the TGF-β signaling pathway  binding pathway that can impair the insulin promoter and cause lower levels of insulin release in beta cells.  Two specific diseases that can result in a mutation to the exocrine pathway (which KLF11 is a part of) are pancreatic cancer and type 2 diabetes.   

NovoTFF-100A; A Fancy Way of Saying Brain Tumor Treatment Made Easy

          The new novocure NovoTFF system was officially announced in a press release one year ago May 29, 2012; today, the therapy data collected over the last year will be announced at the annual Scientific Meeting of the American Society of Clinical Oncology (Sacramento Bee).  The system claims to be the future of tumor reduction treatment, and honestly, it does sound like quite the revolution.  The idea behind the system is much more treatment based than "curing" based.  The treatment "contains" the tumor by creating an electrical field at the site, preventing the cancerous cells from dividing, and therefore, the tumor from growing (Ostrovsky).  The draw to the device is the fact that it is supposed to be used throughout the patient's daily life and will not impede their normal activities.  
          Is this the end all cancer treatment program the the Novocure company claims it to be?  Does it merely extend the patient's life a little longer or does it actually allow for tumor and overall cancer reduction?  These are the questions I hope to explore and attempt to answer.

Saturday, May 26, 2012

The Herpes Virus Strikes Again

        The Herpes virus strikes again, though not in the way you might think. In one of my earlier blog (Who Says Herpes Is All Bad), the Herpes Simplex Virus (HSV) was exposed for being more than a menace but actually an innovative tool for marking cancerous cells with Gaussia Luciferase. This marking enables cancer cells that would normally go undetected to glow and be seen. I came across the article, Targeting HSV-1 virions for specific binding to epidermal growth factor receptor-vIII bearing tumor cells, where Paola Grandi and her fellow researchers have found a way to effectively target and destroy deadly cancerous cells through the use of this multi-faced Herpes Simplex Virus (HSV). Grandi found a way to modify the HSV viral envelope glycoprotein’s, by swapping out the normal heparan sulfate binding domain with a tumor-specific immunotoxin. This immunotoxin, not only has the ability to target this modified virus to the naturally found tumor cell biomarkers, but in other research has also shown the capacity to mediate cell death on its own. This type of immunotherapy is a promising alterative to current methods of treatment, especially with their focus on glioblastoma multiform, one of the “most common primary brain tumors [which] are almost universally fatal despite aggressive therapies, including surgery, radiotherapy, and chemotherapy”(1).

Cancer Related Fatigue in Breast Cancer Patients: Exercise As A Therapy to Decrease the Deregulation of Cellular Energetics

Cancer-related fatigue (CRF) is one of the most prominent and under-discussed symptoms of cancer. 48% of cancer patients experience CRF and 58% to 94% of patients with breast cancer experience CRF while they are undergoing treatment (1). The National Comprehensive Cancer Network defines CRF as “a distressing persistent, subjective sense of physical, emotional and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning” (2). Due to the persistent sense of tiredness unrelated to activity, patients often describe feeling paralyzed by CRF, as it interferes significantly with their quality of life. What I found fascinating was symptoms of CRF could be present after the cancer has been treated up until death, meaning something about the cancer, treatment, or both, caused a long-lasting, if not permanent change in the patient on a molecular level (1). It is also worth noting that breast cancer patients who received chemotherapy and radiation versus radiation alone were more likely to be fatigued years after treatment, showing the type of therapy most definitely influences the duration and severity of CRF (1).

Pertuzumab: Herceptin Resistance Fix?

About a week ago I came across an article that described a woman who was diagnosed with metastatic breast cancer and was told that unfortunately, she did not have much left to live. She, her family, and friends shared the below video of her sharing her story of her fight against breast cancer and plead to Genentech to allow an early release of the drug Pertuzamab on the basis of compassionate use. Fortunately, the drug was planned to enter the market early June, so Genentech granted her plea.
This sparked my interest in the drug Pertuzamab and lead me to find out why this woman saw the drug as her only hope for survival.

Friday, May 25, 2012

Sex Hormone Linked To Thyroid Cancer

I found an interesting review article about how sex hormones might be linked to the development of thyroid cancer. The article is composed of old and recent studies of this hypothesis.The researchers investigated the expression of estrogen receptors α and β on normal and abnormal thyroid tissue and composed tables to determine if estrogen is a contributing factor in tumorigenesis.

Tuesday, May 22, 2012

Cancer: Disease of Death or Disease of Aging

Hello Everyone!
So I recently had an interesting conversation with my Dad on the characteristics of cancer, and we got into an interesting conversation over whether or not cancer is a disease of aging through the lovely discussions we had in class I was able to support the fact that cancer is a disease of aging discussing the accumulation of mutations in cells overtime. I also found a statistic that stated that 50% of diagnosed cancers are of people who are 65 and older and the number is projected to be 70% in 2030.
Now the interesting statistic is that cancer deaths attributes to 13% of deaths worldwide. This does not make it then the disease of death, it just makes it a contributor to death.

But my questions are the following:
1) Wouldn't the fact that cancer is a disease of aging naturally lead it to be the disease of death?
2) What are the reasons for cancer not being the disease of death?

Now my inferences are that cancer is not the disease of death because there are many other diseases that contribute to death, and thus cancer is not the sole contributor therefore not making it the disease of death.
What do you all think? Is cancer a disease of aging or death, or both?
Looking forward to your thoughts! :)

Benzene is a Carcinogen! WHAT?

Hi guys! I feel like every science major in history has at some point heard or talked about benzene. And the common facts are easy; six membered ring, strange stability. Last week in O-Chem we went a bit deeper into what makes benzene tick and what gives it that strange stability. At one point during class, Dr. Carrasco mentioned that benzene was a carcinogen, another pretty common fact. However, when asked what made benzene a carcinogen, Dr. Carrasco answered with "I really don't know exactly why it is a carcinogen."
At that point, my mind screamed out, BLOG POST!

Monday, May 21, 2012

Diagnosing Pancreatic Cancer using a PET Scan

Image Above: Figure A: an anterior view PET scan of torso.  Figure
B: transversal view PET scan of torso.  Figure C: pancreas with the
head of the pancreas almost absorbing all of the tracer.  Figure D:
whole pancreas up taking tracer.  Figure E: Tracer is excreted into
other organs, which cause them to appear on the PET scan (1).  
As of now detection of pancreatic cancer remains as a very difficult task. Pancreatic cancer is often not diagnosed until stage III or IV and the cancer has often already metastasized.  On top of this, most cases of diagnosing pancreatic cancer involve very invasive methods. However, a scan known as positron emission tomography (PET) is a great method for imagery of the body due to its non-invasive nature and can be specified for tissue metabolism (using the tracers) rather than on tissue mass or x- ray absorption. Thus, an increase in glucose metabolism, a hallmark of malignant tumors, can be monitored with a tracer and picked up on a PET scan.  In the case of a pancreas, injecting 2[18F]-fluoro-2-deoxy-D- glucose can be used to detect pancreatic cancer by looking where in the pancreas the highest concentration of the tracer exists (6).    

Friday, May 18, 2012

The Resilience of Melanoma

In class we’ve learned that one of the hallmarks of cancer is resisting cell death. A cancer cell’s resistance to apoptosis and its manipulation of the cell cycle are essentially what make it a cancer cell. In an article titled Apoptosis and Melanoma Chemoresistance, by Maria Soengas and Scott Lowe from the University of Michigan, the specific type of cancer – melanoma, an aggressive skin cancer – is discussed, and its notorious reputation for being resistant to many current chemotherapy mechanisms. Scientists have identified molecules involved with apoptosis, and their alteration in melanoma, and say these are providing new insights into the molecular basis for melanoma chemoresistance. They are now out to develop new strategies to counter these effects and improve in their battle against the disease.

Thursday, May 17, 2012

How Cancer Evolution is Being Used to try to Inhibit Cancer Chemo Resistance and Recurrence

Cancer evolves at a staggering rate. Research is now being done to look into how the mechanism of cancer cells evolve. More recently neoplasms have started to be looked at as their own ecosystem and within this ecosystem different cells that are more and less fit than the others. This new view could help researchers develop drugs that prevent chemoresistance and reoccurrence.

Wednesday, May 16, 2012

Cancer: A Consequence of Aging

Introduction & Background
Dr. Islas often reminds us that cancer is a “reward for living as long as you do.”   Over the weekend, I came across two studies that prove just that.  The first study was conducted by a group of scientists at the Gene Environment Association Studies (GENEVA).  The second study was led by scientists at the National Cancer Institute (NCI).  Both studies found that large chromosomal abnormalities, some of which are correlated with increased risk of cancer, can be detected in a fraction of people without a prior history of cancer.  Sampling from hundreds and thousands of individuals, the scientists also found that alterations in chromosomes increase with age, specifically after the age of 50, and may be associated with an increased risk of cancer. (1)
The GENEVA consortium is sponsored by the National Human Genome Research Institute (NHGRI).  The NCI and the NHGRI are both part of the National Institutes of Health (NIH).
Both studies were published online on May 6, 2012 in Nature Genetics.

Tuesday, May 15, 2012

The Curious Case of Glioblastoma: Back to the Progenitors

Did you ever want to be a super hero? To have the ability to fly, read minds, or travel through time? With much frustration, I realized in my childhood that these powers were not in my metaphorical deck of cards. Unfortunately, the biological mayhem maker, Glioblastoma, has found a way to travel through time. No DeLorean. No Lightning. Just a steady diet of TGFα (Transforming Growth Factor).
Well... sort of through time. Astrocytes are a form of mature glial cells and are part of the brain’s native defense system. In the case of brain injury, they may also be produced from quiescent progenitors and stem cells to fill damaged voids. This is a good thing. This study highlights what is a bad thing and making efficient treatment of Glioblastoma Multiform extremely difficult. Researchers found that prolonged exposure to TGF promotes the conversion of “adult” astrocytes into neural progenitors and then stem cells (like the ones mentioned above). This is called anaplasia, and is a daunting characteristic of Glioblastoma Multiform (GBM, Stage IV glioma). These cells violate a critical feature of healthy brain function: absolute control over cellular replication.

Extending the Life of Glioblastoma Patients: Gene-Modified Therapy

In a recent article posted by the Fred Hutchinson Cancer Research Center, a novel therapy is shown to improve the length of survival of patients with high-risk forms of glioblastoma. After looking at the primary research article, I noticed the researchers used many of the principals associated with personalized and targeted therpies we've recently discussed in class. But first, a little background information on glioblastoma.

According to Maciej Mrugala, the study's lead neuro oncologist, "glioblastoma remains one of the most devastating cancers with a median survival of only 12-15 months" (1). The current treatment strategy is to surgically dissect the tumor if possible, and then to treat the patient with a combination of radiation and chemotherapy. While the treatments are effective at killing the tumor, the side effects are often so severe that dosages must be reduced or treatments completely suspended. This results in less effective treatment and the faster death of the patient. However, it looks as if Adair and colleagues have developed a treatment that circumvents the common problem of toxicity and suppression of blood stem cells (HSCs).

Not all tumor cells are created equal

Introduction & Background
Stefanie Jeffrey, MD (2)
Earlier in the quarter Dr. Islas taught us that three lines of evidence – biochemical, immunological, and cytogenetic – suggested tumors are monoclonal growths.  Recall in a monoclonal growth, a single cell transforms from normal to malignant and subsequently gives rise to a tumor composed of genetically identical cells.  Together, the three experiments, from different fields, provided strong support that cancer arises from a single progenitor cell gone awry.
Alternatively, a tumor can be polyclonal in origin. In this case, multiple cells transform from normal to malignant, leading to a tumor mass composed of genetically distinct sub-populations of cells. (1) (Fig. 1)
Over the weekend, I came across a study conducted by a group of Stanford scientist who have discovered that cancer cells shed by a single tumor into the bloodstream are genetically diverse.  Some cancer cells have turned on genes that make them more adept at lodging themselves in new places, aiding in their ability to metastasize to new organs (2).  Other cancer cells have an entirely different pattern of gene expression.
The senior author of the study is Stefanie Jeffrey, MD, professor of surgery and chief of surgical oncology research at the Stanford University School of Medicine.  The research was published in PLoS ONE on May 7, 2012.